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Review Article

Multiple human single-stranded DNA binding proteins function in genome maintenance: structural, biochemical and functional analysis

, &
Pages 98-116 | Received 05 Feb 2009, Accepted 25 Feb 2009, Published online: 01 Jun 2009

References

  • Abraham RT. 2001. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15:2177–2196.
  • Adachi Y, and Laemmli UK. 1992. Identification of nuclear pre-replication centers poised for DNA synthesis in Xenopus egg extracts: immunolocalization study of replication protein A. J Cell Biol 119:1–15.
  • Anantha RW, Sokolova E, and Borowiec JA. 2008. RPA phosphorylation facilitates mitotic exit in response to mitotic DNA damage. Proc Natl Acad Sci USA 105:12903–12908.
  • Arcus V. 2002. OB-fold domains: a snapshot of the evolution of sequence, structure and function. Curr Opin Struct Biol 12:794–801.
  • Arunkumar AI, Stauffer ME, Bochkareva E, Bochkarev A, and Chazin WJ. 2003. Independent and coordinated functions of replication protein A tandem high affinity single-stranded DNA binding domains. J Biol Chem 278:41077–41082.
  • Bae SH, and Seo YS. 2000. Characterization of the enzymatic properties of the yeast dna2 Helicase/endonuclease suggests a new model for Okazaki fragment processing. J Biol Chem 275:38022–39031.
  • Bae SH, Bae KH, Kim JA, and Seo YS. 2001. RPA governs endonuclease switching during processing of Okazaki fragments in eukaryotes. Nature 412:456–461.
  • Ball HL, Myers JS, and Cortez D. 2005. ATRIP binding to replication protein A-single-stranded DNA promotes ATR-ATRIP localization but is dispensable for Chk1 phosphorylation. Mol Biol Cell 16:2372–2381.
  • Batty DP, and Wood RD. 2000. Damage recognition in nucleotide excision repair of DNA. Gene 241:193–204.
  • Batty D, Rapic’-Otrin V, Levine AS, and Wood RD. 2000. Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol 300:275–290.
  • Bell SP, and Dutta A. 2002. DNA replication in eukaryotic cells. Annu Rev Biochem 71:333–374.
  • Bernstein DA, Eggington JM, Killoran MP, Misic AM, Cox MM, and Keck JL. 2004. Crystal structure of the Deinococcus radiodurans single-stranded DNA-binding protein suggests a mechanism for coping with DNA damage. Proc Natl Acad Sci USA 101:8575–8580.
  • Bessho T, Sancar A, Thompson LH, and Thelen MP. 1997. Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex. J Biol Chem 272:3833–3837.
  • Binz SK, Lao Y, Lowry DF, and Wold MS. 2003. The phosphorylation domain of the 32-kDa subunit of replication protein A (RPA) modulates RPA-DNA interactions. Evidence for an intersubunit interaction. J Biol Chem 278:35584–35591.
  • Blackwell LJ, Borowiec JA, and Masrangelo IA. 1996. Single-stranded-DNA binding alters human replication protein A structure and facilitates interaction with DNA-dependent protein kinase. Mol Cell Biol 16:4798–4807.
  • Bochkarev A, and Bochkareva E. 2004. From RPA to BRCA2: lessons from single-stranded DNA binding by the OB-fold. Curr Opin Struct Biol 14:36–42.
  • Bochkarev A, Pfuetzner RA, Edwards AM, and Frappier L. 1997. Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA. Nature 385:176–181.
  • Bochkareva E, Korolev S, Lees-Miller SP, and Bochkarev A. 2002. Structure of the RPA trimerization core and its role in the multistep DNA-binding mechanism of RPA. Embo J 21:1855–1863.
  • Bork P, Blomberg N, and Nilges M. 1996. Internal repeats in the BRCA2 protein sequence. Nat Genet 13:22–23.
  • Borowiec JA, Dean FB, Bullock PA, and Hurwitz J. 1990. Binding and unwinding – how T antigen engages the SV40 origin of DNA replication. Cell 60:181–184.
  • Brosh Jr RM, Orren DK, Nehlin JO, Ravn PH, Kenny MK, Machwe A, and Bohr VA. 1999. Functional and physical interaction between WRN helicase and human replication protein A. J Biol Chem 274:18341–18350.
  • Brosh Jr RM, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, and Bohr VA. 2000. Replication protein A physically interacts with the Bloom’s syndrome protein and stimulates its helicase activity. J Biol Chem 275:23500–23508.
  • Brush GS, Anderson CW, and Kelly TJ. 1994. The DNA-activated protein kinase is required for the phosphorylation of replication protein A during simian virus 40 DNA replication. Proc Natl Acad Sci USA 91:12520–12524.
  • Budzowska M, and Kanaar R. 2009. Mechanisms of dealing with DNA damage-induced replication problems. Cell Biochem Biophys 53:17–31.
  • Bugreev DV, Yu X, Egelman EH, and Mazin AV. 2007. Novel pro- and anti-recombination activities of the Bloom’s syndrome helicase. Genes Dev 21:3085–3094.
  • Bujalowski W, and Lohman TM. 1986. Escherichia coli single-strand binding protein forms multiple, distinct complexes with single-stranded DNA. Biochemistry 25:7799–7802.
  • Bujalowski W, Overman LB, and Lohman TM. 1988. Binding mode transitions of Escherichia coli single strand binding protein-single-stranded DNA complexes. Cation, anion, pH, and binding density effects. J Biol Chem 263:4629–4640.
  • Burgers PM. 2009. Polymerase dynamics at the eukaryotic DNA replication fork J Biol Chem 284:4041–4045.
  • Cahill D, Connor B, and Carney JP. 2006. Mechanisms of eukaryotic DNA double strand break repair. Front Biosci 11:1958–1976.
  • Carty MP, Zernik-Kobak M, McGrath S, and Dixon K. 1994. UV light-induced DNA synthesis arrest in HeLa cells is associated with changes in phosphorylation of human single-stranded DNA-binding protein. Embo J 13:2114–2123.
  • Casas-Finet JR, Khamis MI, Maki AH, and Chase JW. 1987a. Tryptophan 54 and phenylalanine 60 are involved synergistically in the binding of E. coli SSB protein to single-stranded polynucleotides. FEBS Lett 220:347–352.
  • Casas-Finet JR, Khamis MI, Maki AH, Ruvolo PP, and Chase JW. 1987b. Optically detected magnetic resonance of tryptophan residues in Escherichia coli ssb gene product and E. coli plasmid-encoded single-stranded DNA-binding proteins and their complexes with poly(deoxythymidylic) acid. J Biol Chem 262:8574–8583.
  • Chaganti RS, Schonberg S, and German J. 1974. A manyfold increase in sister chromatid exchanges in Bloom’s syndrome lymphocytes. Proc Natl Acad Sci USA 71:4508–4512.
  • Chan DW, Son SC, Block W, Ye R, Khanna KK, Wold MS, Douglas P, Goodarzi AA, Pelley J, Taya Y, Lavin MF, and Lees-Miller SP. 2000. Purification and characterization of ATM from human placenta. A manganese-dependent, wortmannin-sensitive serine/threonine protein kinase. J Biol Chem 275:7803–7810.
  • Chen L, Nievera CJ, Lee AY, and Wu X. 2008. Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair. J Biol Chem 283:7713–7720.
  • Chen PL, Chen CF, Chen Y, Xiao J, Sharp ZD, and Lee WH. 1998. The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment. Proc Natl Acad Sci USA 95:5287–5292.
  • Coleman TR, Carpenter PB, and Dunphy WG. 1996. The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA replication in cell-free extracts. Cell 87:53–63.
  • Conaway RC, and Lehman IR. 1982a. A DNA primase activity associated with DNA polymerase alpha from Drosophila melanogaster embryos. Proc Natl Acad Sci USA 79:2523–2527.
  • Conaway RC, and Lehman IR. 1982b. Synthesis by the DNA primase of Drosophila melanogaster of a primer with a unique chain length. Proc Natl Acad Sci USA 79:4585–4588.
  • Constantinou A, Tarsounas M, Karow JK, Brosh RM, Bohr VA, Hickson ID, and West SC. 2000. Werner’s syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO Rep 1:80–84.
  • Coue M, Kearsey SE, and Mechali M. 1996. Chromotin binding, nuclear localization and phosphorylation of Xenopus cdc21 are cell-cycle dependent and associated with the control of initiation of DNA replication. Embo J 15:1085–1097.
  • Coverley D, Kenny MK, Munn M, Rupp WD, Lane DP, and Wood RD. 1991. Requirement for the replication protein SSB in human DNA excision repair. Nature 349:538–541.
  • Coverley D, Kenny MK, Lane DP, and Wood RD. 1992. A role for the human single-stranded DNA binding protein HSSB/RPA in an early stage of nucleotide excision repair. Nucleic Acids Res 20:3873–3880.
  • Crespan E, Hubscher U, and Maga G. 2007. Error-free bypass of 2-hydroxyadenine by human DNA polymerase lambda with Proliferating Cell Nuclear Antigen and Replication Protein A in different sequence contexts. Nucleic Acids Res 35:5173–5181.
  • Curth U, Greipel J, Urbanke C, and Maass G. 1993. Multiple binding modes of the single-stranded DNA binding protein from Escherichia coli as detected by tryptophan fluorescence and site-directed mutagenesis. Biochemistry 32:2585–2591.
  • Cuvier O, Lutzmann M, and Mechali M. 2006. ORC is necessary at the interphase-to-mitosis transition to recruit cdc2 kinase and disassemble RPA foci. Curr Biol 16:516–523.
  • Davies AA, Huttner D, Daigaku Y, Chen S, and Ulrich HD. 2008. Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a. Mol Cell 29:625–636.
  • Davis AP, and Symington LS. 2003. The Rad52-Rad59 complex interacts with Rad51 and replication protein A. DNA Repair (Amst) 2:1127–1134.
  • Davydova EK, and Rothman-Denes LB. 2003. Escherichia coli single-stranded DNA-binding protein mediates template recycling during transcription by bacteriophage N4 virion RNA polymerase. Proc Natl Acad Sci USA 100:9250–9255.
  • Dean FB, Bullock P, Murakami Y, Wobbe CR, Weissbach L, and Hurwitz J. 1987. Simian virus 40 (SV40) DNA replication: SV40 large T antigen unwinds DNA containing the SV40 origin of replication. Proc Natl Acad Sci USA 84:16–20.
  • de Jager M, van Noort J, van Gent DC, Dekker C, Kanaar R, and Wyman C. 2001. Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Mol Cell 8:1129–1135.
  • de Laat WL, Appeldoorn E, Sugasawa K, Weterings E, Jaspers NG, and Hoeijmakers JH. 1998. DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair. Genes Dev 12:2598–2609.
  • Dimitrova DS, and Gilbert DM. 2000a. Stability and nuclear distribution of mammalian replication protein A heterotrimeric complex. Exp Cell Res 254:321–327.
  • Dimitrova DS, and Gilbert DM. 2000b. Temporally coordinated assembly and disassembly of replication factories in the absence of DNA synthesis. Nat Cell Biol 2:686–694.
  • Dimitrova DS, Todorov IT, Melendy T, and Gilbert DM. 1999. Mcm2, but not RPA, is a component of the mammalian early G1-phase prereplication complex. J Cell Biol 146:709–722.
  • Din S, Brill SJ, Fairman MP, and Stillman B. 1990. Cell-cycle-regulated phosphorylation of DNA replication factor A from human and yeast cells. Genes Dev 4:968–977.
  • Doherty KM, Sommers JA, Gray MD, Lee JW, von Kobbe C, Thoma NH, Kureekattil RP, Kenny MK, and Brosh Jr RM. 2005. Physical and functional mapping of the replication protein a interaction domain of the werner and bloom syndrome helicases. J Biol Chem 280:29494–29505.
  • Dutta A, and Stillman B. 1992. cdc2 family kinases phosphorylate a human cell DNA replication factor, RPA, and activate DNA replication. Embo J 11:2189–2199.
  • Epstein CJ, Martin GM, Schultz AL, and Motulsky AG. 1966. Werner’s syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore) 45:177–221.
  • Evans E, Moggs JG, Hwang JR, Egly JM, and Wood RD. 1997. Mechanism of open complex and dual incision formation by human nucleotide excision repair factors. Embo J 16:6559–6573.
  • Fairman MP, and Stillman B. 1988. Cellular factors required for multiple stages of SV40 DNA replication in vitro. Embo J 7:1211–1218.
  • Fang F, and Newport JW. 1993. Distinct roles of cdk2 and cdc2 in RP-A phosphorylation during the cell cycle. J Cell Sci 106(Pt 3):983–994.
  • Fanning E, Klimovich V, and Nager AR. 2006. A dynamic model for replication protein A (RPA) function in DNA processing pathways. Nucleic Acids Res 34:4126–4137.
  • Ferrari ME, Bujalowski W, and Lohman TM. 1994. Co-operative binding of Escherichia coli SSB tetramers to single-stranded DNA in the (SSB)35 binding mode. J Mol Biol 236:106–123.
  • Forterre P, and Philippe H. 1999. The last universal common ancestor (LUCA), simple or complex? Biol Bull 196:373–375; discussion 375–377.
  • Fotedar R, and Roberts JM. 1992. Cell cycle regulated phosphorylation of RPA-32 occurs within the replication initiation complex. Embo J 11:2177–2187.
  • Francon P, Lemaitre JM, Dreyer C, Maiorano D, Cuvier O, and Mechali M. 2004. A hypophosphorylated form of RPA34 is a specific component of pre-replication centers. J Cell Sci 117:4909–4920.
  • Freudenreich CH. 2007. Chromosome fragility: molecular mechanisms and cellular consequences. Front Biosc. 12:4911–4924.
  • Frick DN, and Richardson CC. 2001. DNA primases. Annu Rev Biochem 70:39–80.
  • Fukuchi K, Martin GM, and Monnat Jr RJ. 1989. Mutator phenotype of Werner syndrome is characterized by extensive deletions. Proc Natl Acad Sci USA 86:5893–5897.
  • Garg P, and Burgers PM. 2005. DNA polymerases that propagate the eukaryotic DNA replication fork. Crit Rev Biochem Mol Biol 40:115–128.
  • Gascon I, Lazaro JM, and Salas M. 2000. Differential functional behavior of viral phi29, Nf and GA-1 SSB proteins. Nucleic Acids Res 28:2034–2042.
  • Gately DP, Hittle JC, Chan GK, and Yen TJ. 1998. Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity. Mol Biol Cell 9:2361–2374.
  • Godthelp BC, Artwert F, Joenje H, and Zdzienicka MZ. 2002. Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1. Oncogene 21:5002–5005.
  • Gomes XV, Henricksen LA, and Wold MS. 1996. Proteolytic mapping of human replication protein A: evidence for multiple structural domains and a conformational change upon interaction with single-stranded DNA. Biochemistry 35:5586–5595.
  • Griffith JD, Harris LD, and Register 3rd J. 1984. Visualization of SSB-ssDNA complexes active in the assembly of stable RecA-DNA filaments. Cold Spring Harb Symp Quant Biol 49:553–559.
  • Grompe M, and D’Andrea A. 2001. Fanconi anemia and DNA repair. Hum Mol Genet 10:2253–2259.
  • Gupta R, Sharma S, Sommers JA, Kenny MK, Cantor SB, and Brosh Jr RM. 2007. FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein. Blood 110:2390–2398.
  • Guzder SN, Habraken Y, Sung P, Prakash L, and Prakash S. 1995. Reconstitution of yeast nucleotide excision repair with purified Rad proteins, replication protein A, and transcription factor TFIIH. J Biol Chem 270:12973–12976.
  • He Z, Henricksen LA, Wold MS, and Ingles CJ. 1995. RPA involvement in the damage-recognition and incision steps of nucleotide excision repair. Nature 374:566–569.
  • Heller RC, and Marians KJ. 2006a. Replication fork reactivation downstream of a blocked nascent leading strand. Nature 439:557–562.
  • Heller RC, and Marians KJ. 2006b. Replisome assembly and the direct restart of stalled replication forks. Nat Rev Mol Cell Biol 7:932–943.
  • Henricksen LA, and Wold MS. 1994. Replication protein A mutants lacking phosphorylation sites for p34cdc2 kinase support DNA replication. J Biol Chem 269:24203–24208.
  • Henricksen LA, Carter T, Dutta A, and Wold MS. 1996. Phosphorylation of human replication protein A by the DNA-dependent protein kinase is involved in the modulation of DNA replication. Nucleic Acids Res 24:3107–3112.
  • Hua XH, and Newport J. 1998. Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2. J Cell Biol 140:271–281.
  • Hurwitz J, Dean FB, Kwong AD, and Lee SH. 1990. The in vitro replication of DNA containing the SV40 origin. J Biol Chem 265:18043–18046.
  • Iftode C, and Borowiec JA. 2000. 5’; 3’ molecular polarity of human replication protein A (hRPA) binding to pseudo-origin DNA substrates. Biochemistry 39:11970–11981.
  • Iftode C, Daniely Y, and Borowiec JA. 1999. Replication protein A (RPA): the eukaryotic SSB. Crit Rev Biochem Mol Biol 34:141–180.
  • Jackson D, Dhar K, Wahl JK, Wold MS, and Borgstahl GE. 2002. Analysis of the human replication protein A:Rad52 complex: evidence for crosstalk between RPA32, RPA70, Rad52 and DNA. J Mol Biol 321:133–148.
  • Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, and Jackson SP. 2006. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8:37–45.
  • Kannouche PL, Wing J, and Lehmann AR. 2004. Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Mol Cell 14:491–500.
  • Karow JK, Chakraverty RK, and Hickson ID. 1997. The Bloom’s syndrome gene product is a 3’–5’ DNA helicase. J Biol Chem 272:30611–30614.
  • Kelly TJ, Simancek P, and Brush GS. 1998. Identification and characterization of a single-stranded DNA-binding protein from the archaeon Methanococcus jannaschii. Proc Natl Acad Sci USA 95:14634–14639.
  • Kenny MK, Lee SH, and Hurwitz J. 1989. Multiple functions of human single-stranded-DNA binding protein in simian virus 40 DNA replication: single-strand stabilization and stimulation of DNA polymerases alpha and delta. Proc Natl Acad Sci USA 86:9757–9761.
  • Kenny MK, Schlegel U, Furneaux H, and Hurwitz J. 1990. The role of human single-stranded DNA binding protein and its individual subunits in simian virus 40 DNA replication. J Biol Chem 265:7693–7700.
  • Kerr ID, Wadsworth RI, Cubeddu L, Blankenfeldt W, Naismith JH, and White MF. 2003. Insights into ssDNA recognition by the OB fold from a structural and thermodynamic study of Sulfolobus SSB protein. Embo J 22:2561–2570.
  • Khamis MI, Casas-Finet JR, and Maki AH. 1987a. Stacking interactions of tryptophan residues and nucleotide bases in complexes formed between Escherichia coli single-stranded DNA binding protein and heavy atom-modified poly(uridylic) acid. A study by optically detected magnetic resonance spectroscopy. J Biol Chem 262:1725–1733.
  • Khamis MI, Casas-Finet JR, Maki AH, Murphy JB, and Chase JW. 1987b. Role of tryptophan 54 in the binding of E. coli single-stranded DNA-binding protein to single-stranded polynucleotides. FEBS Lett 211:155–159.
  • Khanna KK, and Jackson SP. 2001. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27:247–254.
  • Kim C, Snyder RO, and Wold MS. 1992. Binding properties of replication protein A from human and yeast cells. Mol Cell Biol 12:3050–3059.
  • Kim C, Paulus BF, and Wold MS. 1994. Interactions of human replication protein A with oligonucleotides. Biochemistry 33:14197–14206.
  • Kim C, and Wold MS. 1995. Recombinant human replication protein A binds to polynucleotides with low cooperativity. Biochemistry 34:2058–2064.
  • Kim DK, Stigger E, and Lee SH. 1996. Role of the 70-kDa subunit of human replication protein A (I). Single-stranded dna binding activity, but not polymerase stimulatory activity, is required for DNA replication. J Biol Chem 271:15124–15129.
  • Kolodner RD, Putnam CD, and Myung K. 2002. Maintenance of genome stability in Saccharomyces cerevisiae. Science. 297:552–557.
  • Kolpashchikov DM, Khodyreva SN, Khlimankov DY, Wold MS, Favre A, and Lavrik OI. 2001. Polarity of human replication protein A binding to DNA. Nucleic Acids Res 29:373–379.
  • Krasikova YS, Belousova EA, Lebedeva NA, Pestryakov PE, and Lavrik OI. 2008. Interaction between DNA polymerase lambda and RPA during translesion synthesis. Biochemistry (Mosc) 73:1042–1046.
  • Krejci L, Van Komen S, Li Y, Villemain J, Reddy MS, Klein H, Ellenberger T, and Sung P. 2003. DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature 423:305–309.
  • Krogh BO, and Symington LS. 2004. Recombination proteins in yeast. Annu Rev Genet 38:233–271.
  • Kumagai A, Kim SM, and Dunphy WG. 2004. Claspin and the activated form of ATR-ATRIP collaborate in the activation of Chk1. J Biol Chem 279:49599–49608.
  • Kumagai A, Lee J, Yoo HY, and Dunphy WG. 2006. TopBP1 activates the ATR-ATRIP complex. Cell 124:943–955.
  • Kumaran S, Kozlov AG, and Lohman TM. 2006. Saccharomyces cerevisiae replication protein A binds to single-stranded DNA in multiple salt-dependent modes. Biochemistry 45:11958–11973.
  • Kunkel TA, Pavlov YI, and Bebenek K. 2003. Functions of human DNA polymerases eta, kappa and iota suggested by their properties, including fidelity with undamaged DNA templates. DNA Repair (Amst) 2:135–149.
  • Lee DG, Makhov AM, Klemm RD, Griffith JD, and Bell SP. 2000. Regulation of origin recognition complex conformation and ATPase activity: differential effects of single-stranded and double-stranded DNA binding. Embo J 19:4774–4782.
  • Lee SH, Kim DK, and Drissi R. 1995. Human xeroderma pigmentosum group A protein interacts with human replication protein A and inhibits DNA replication. J Biol Chem 270:21800–21805.
  • Li L, Lu X, Peterson CA, and Legerski RJ. 1995. An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair. Mol Cell Biol 15:5396–5402.
  • Li X, and Heyer WD. 2008. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res 18:99–113.
  • Lin SY, Li K, Stewart GS, and Elledge SJ. 2004. Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation. Proc Natl Acad Sci USA 101:6484–6489.
  • Lin XH, Walter J, Scheidtmann K, Ohst K, Newport J, and Walter G. 1998. Protein phosphatase 2A is required for the initiation of chromosomal DNA replication. Proc Natl Acad Sci USA 95:14693–14698.
  • Lisby M, Barlow JH, Burgess RC and. Rothstein R. 2004. Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell 118:699–713.
  • Liu VF, and Weaver DT. 1993. The ionizing radiation-induced replication protein A phosphorylation response differs between ataxia telangiectasia and normal human cells. Mol Cell Biol 13:7222–7231.
  • Liu Y, Yang Z, Utzat CD, Liu Y, Geacintov NE, Basu AK, and Zou Y. 2005. Interactions of human replication protein A with single-stranded DNA adducts. Biochem J 385:519–526.
  • Lohman TM, and Ferrari ME. 1994. Escherichia coli single-stranded DNA-binding protein: multiple DNA-binding modes and cooperativities. Annu Rev Biochem 63:527–570.
  • Lohman TM, and Overman LB. 1985. Two binding modes in Escherichia coli single strand binding protein-single stranded DNA complexes. Modulation by NaCl concentration. J Biol Chem 260:3594–3603.
  • Lohman TM, Overman LB, and Datta S. 1986. Salt-dependent changes in the DNA binding co-operativity of Escherichia coli single strand binding protein. J Mol Biol 187:603–615.
  • Lohman TM, Bujalowski W, Overman LB, and Wei TF. 1988. Interactions of the E. coli single strand binding (SSB) protein with ss nucleic acids. Binding mode transitions and equilibrium binding studies. Biochem Pharmacol 37:1781–1782.
  • Luo G, Santoro IM, McDaniel LD, Nishijima I, Mills M, Youssoufian H, Vogel H, Schultz RA, and Bradley A. 2000. Cancer predisposition caused by elevated mitotic recombination in Bloom mice. Nat Genet 26:424–429.
  • Maga G, and Hubscher U. 1996. DNA replication machinery: functional characterization of a complex containing DNA polymerase alpha, DNA polymerase delta, and replication factor C suggests an asymmetric DNA polymerase dimer. Biochemistry 35:5764–5777.
  • Maga G, Frouin I, Spadari S, and Hubscher U. 2001. Replication protein A as a “fidelity clamp” for DNA polymerase alpha. J Biol Chem 276:18235–18242.
  • Maga G, Villani G, Crespan E, Wimmer U, Ferrari E, Bertocci B, and Hubscher U. 2007. 8-oxo-guanine bypass by human DNA polymerases in the presence of auxiliary proteins. Nature 447:606–608.
  • Manthey KC, Opiyo S, Glanzer JG, Dimitrova D, Elliott J, and Oakley GG. 2007. NBS1 mediates ATR-dependent RPA hyperphosphorylation following replication-fork stall and collapse. J Cell Sci 120:4221–4229.
  • Marston NJ, Richards WJ, Hughes D, Bertwistle D, Marshall CJ, and Ashworth A. 1999. Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals. Mol Cell Biol 19:4633–4642.
  • Martin GM, Sprague CA, and Epstein CJ. 1970. Replicative life-span of cultivated human cells. Effects of donor’s age, tissue, and genotype. Lab Invest 23:86–92.
  • Matsuda T, Saijo M, Kuraoka I, Kobayashi T, Nakatsu Y, Nagai A, Enjoji T, Masutani C, Sugasawa K, Hanaoka F, Yasui A, and Tanaka K. 1995. DNA repair protein XPA binds replication protein A (RPA). J Biol Chem 270:4152–4157.
  • Matsumoto T, Morimoto Y, Shibata N, Kinebuchi T, Shimamoto N, Tsukihara T, and Yasuoka N. 2000. Roles of functional loops and the C-terminal segment of a single-stranded DNA binding protein elucidated by X-Ray structure analysis. J Biochem 127:329–335.
  • Matsunaga T, Park CH, Bessho T, Mu D, and Sancar A. 1996. Replication protein A confers structure-specific endonuclease activities to the XPF-ERCC1 and XPG subunits of human DNA repair excision nuclease. J Biol Chem 271:11047–11050.
  • McIlwraith MJ, Van Dyck E, Masson JY, Stasiak AZ, Stasiak A, and West SC. 2000. Reconstitution of the strand invasion step of double-strand break repair using human Rad51 Rad52 and RPA proteins. J Mol Biol 304:151–164.
  • Mer G, Bochkarev A, Gupta R, Bochkareva E, Frappier L, Ingles CJ, Edwards AM, and Chazin WJ. 2000. Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA. Cell 103:449–456.
  • Merrill BM, Williams KR, Chase JW, and Konigsberg WH. 1984. Photochemical cross-linking of the Escherichia coli single-stranded DNA-binding protein to oligodeoxynucleotides. Identification of phenylalanine 60 as the site of cross-linking. J Biol Chem 259:10850–10856.
  • Meyer RR, and Laine PS. 1990. The single-stranded DNA-binding protein of Escherichia coli. Microbiol Rev 54:342–380.
  • Michel B, Grompone G, Flores MJ, and Bidnenko V. 2004. Multiple pathways process stalled replication forks. Proc Natl Acad Sci USA 101:12783–12788.
  • Milne GT, and Weaver DT. 1993. Dominant negative alleles of RAD52 reveal a DNA repair/recombination complex including Rad51 and Rad52. Genes Dev 7:1755–1765.
  • Mimura S, and Takisawa H. 1998. Xenopus Cdc45-dependent loading of DNA polymerase alpha onto chromatin under the control of S-phase Cdk. Embo J 17:5699–5707.
  • Mimura S, Masuda T, Matsui T, and Takisawa H. 2000. Central role for cdc45 in establishing an initiation complex of DNA replication in Xenopus egg extracts. Genes Cells 5:439–452.
  • Mitsis PG, Kowalczykowski SC, and Lehman IR. 1993. A single-stranded DNA binding protein from Drosophila melanogaster: characterization of the heterotrimeric protein and its interaction with single-stranded DNA. Biochemistry 32:5257–5266.
  • Mu D, Park CH, Matsunaga T, Hsu DS, Reardon JT, and Sancar A. 1995. Reconstitution of human DNA repair excision nuclease in a highly defined system. J Biol Chem 270:2415–2418.
  • Mu D, Wakasugi M, Hsu DS, and Sancar A. 1997. Characterization of reaction intermediates of human excision repair nuclease. J Biol Chem 272:28971–28979.
  • Murzin AG. 1993. OB(oligonucleotide/oligosaccharide binding)-fold: common structural and functional solution for non-homologous sequences. Embo J 12:861–867.
  • Myers JS, and Cortez D. 2006. Rapid activation of ATR by ionizing radiation requires ATM and Mre11. J Biol Chem 281:9346–9350.
  • Niu H, Erdjument-Bromage H, Pan ZQ, Lee SH, Tempst P, and Hurwitz J. 1997. Mapping of amino acid residues in the p34 subunit of human single-stranded DNA-binding protein phosphorylated by DNA-dependent protein kinase and Cdc2 kinase in vitro. J Biol Chem 272:12634–12641.
  • Oakley GG, Patrick SM, Yao J, Carty MP, Turchi JJ, and Dixon K. 2003. RPA phosphorylation in mitosis alters DNA binding and protein–protein interactions. Biochemistry 42:3255–3264.
  • Olson E, Nievera CJ, Klimovich V, Fanning E, and Wu X. 2006. RPA2 is a direct downstream target for ATR to regulate the S-phase checkpoint. J Biol Chem 281:39517–39533.
  • Overman LB, and Lohman TM. 1994. Linkage of pH, anion and cation effects in protein–nucleic acid equilibria. Escherichia coli SSB protein–single stranded nucleic acid interactions. J Mol Biol 236:165–178.
  • Overman LB, Bujalowski W, and Lohman TM. 1988. Equilibrium binding of Escherichia coli single-strand binding protein to single-stranded nucleic acids in the (SSB)65 binding mode. Cation and anion effects and polynucleotide specificity. Biochemistry 27:456–471.
  • Pan ZQ, Amin AA, Gibbs E, Niu H, and Hurwitz J. 1994. Phosphorylation of the p34 subunit of human single-stranded-DNA-binding protein in cyclin A-activated G1 extracts is catalyzed by cdk-cyclin A complex and DNA-dependent protein kinase. Proc Natl Acad Sci USA 91:8343–8347.
  • Pan ZQ, Park CH, Amin AA, Hurwitz J, and Sancar A. 1995. Phosphorylated and unphosphorylated forms of human single-stranded DNA-binding protein are equally active in simian virus 40 DNA replication and in nucleotide excision repair. Proc Natl Acad Sci USA 92:4636–4640.
  • Paques F, and Haber JE. 1999. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63:349–404.
  • Park JS, Park SJ, Peng X, Wang M, Yu MA, and Lee SH. 1999a. Involvement of DNA-dependent protein kinase in UV-induced replication arrest. J Biol Chem 274:32520–32527.
  • Park JS, Wang M, Park SJ, and Lee SH. 1999b. Zinc finger of replication protein A, a non-DNA binding element, regulates its DNA binding activity through redox. J Biol Chem 274:29075–29080.
  • Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, and Venkitaraman AR. 2002. Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature 420:287–293.
  • Pestryakov PE, Khlimankov DY, Bochkareva E, Bochkarev A, and Lavrik OI. 2004. Human replication protein A (RPA) binds a primer-template junction in the absence of its major ssDNA-binding domains. Nucleic Acids Res 32:1894–1903.
  • Pfuetzner RA, Bochkarev A, Frappier L, and Edwards AM. 1997. Replication protein A. Characterization and crystallization of the DNA binding domain. J Biol Chem 272:430–434.
  • Philipova D, Mullen JR, Maniar HS, Lu J, Gu C, and Brill SJ. 1996. A hierarchy of SSB protomers in replication protein A. Genes Dev 10:2222–2233.
  • Pichierri P, Franchitto A, and Rosselli F. 2004. BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks. Embo J 23:3154–3163.
  • Raghunathan S, Ricard CS, Lohman TM, and Waksman G. 1997. Crystal structure of the homo-tetrameric DNA binding domain of Escherichia coli single-stranded DNA-binding protein determined by multiwavelength x-ray diffraction on the selenomethionyl protein at 2.9-A resolution. Proc Natl Acad Sci USA 94:6652–6657.
  • Raghunathan S, Kozlov AG, Lohman TM, and Waksman G. 2000. Structure of the DNA binding domain of E. coli SSB bound to ssDNA. Nat Struct Biol 7:648–652.
  • Richard DJ, Bell SD, and White MF. 2004. Physical and functional interaction of the archaeal single-stranded DNA-binding protein SSB with RNA polymerase. Nucleic Acids Res 32:1065–1074.
  • Richard DJ, Bolderson E, Cubeddu L, Wadsworth RI, Savage K, Sharma GG, Nicolette ML, Tsvetanov S, McIlwraith MJ, Pandita RK, White MF, and Khanna KK. 2008. Single-stranded DNA-binding protein hSSB1 is critical for genomic stability. Nature 453:677–681.
  • Robison JG, Elliott J, Dixon K, and Oakley GG. 2004. Replication protein A and the Mre11.Rad50.Nbs1 complex co-localize and interact at sites of stalled replication forks. J Biol Chem 279:34802–34810.
  • Rowles A, Chong JP, Brown L, Howell M, Evan GI, and Blow JJ. 1996. Interaction between the origin recognition complex and the replication licensing system in Xenopus. Cell 87:287–296.
  • Sakamoto S, Nishikawa K, Heo SJ, Goto M, Furuichi Y, and Shimamoto A. 2001. Werner helicase relocates into nuclear foci in response to DNA damaging agents and co-localizes with RPA and Rad51. Genes Cells 6:421–430.
  • Sanz MM, Proytcheva M, Ellis NA, Holloman WK, and German J. 2000. BLM, the Bloom’s syndrome protein, varies during the cell cycle in its amount, distribution, and co-localization with other nuclear proteins. Cytogenet Cell Genet 91:217–223.
  • Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, and Jackson SP. 2007. Human CtIP promotes DNA end resection. Nature 450:509–514.
  • Savvides SN, Raghunathan S, Futterer K, Kozlov AG, Lohman TM, and Waksman G. 2004. The C-terminal domain of full-length E. coli SSB is disordered even when bound to DNA. Protein Sci 13:1942–1947.
  • Shamoo Y, Friedman AM, Parsons MR, Konigsberg WH, and Steitz TA. 1995. Crystal structure of a replication fork single-stranded DNA binding protein (T4 gp32) complexed to DNA. Nature 376:362–366.
  • Shao RG, Cao CX, Zhang H, Kohn KW, Wold MS, and Pommier Y. 1999. Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes. Embo J 18:1397–1406.
  • Shen JC, Lao Y, Kamath-Loeb A, Wold MS, and Loeb LA. 2003. The N-terminal domain of the large subunit of human replication protein A binds to Werner syndrome protein and stimulates helicase activity. Mech Ageing Dev 124:921–930.
  • Shen Z, Cloud KG, Chen DJ, and Park MS. 1996. Specific interactions between the human RAD51 and RAD52 proteins. J Biol Chem 271:148–152.
  • Shereda RD, Kozlov AG, Lohman TM, Cox MM and. Keck JL. 2008. SSB as an organizer/mobilizer of genome maintenance complexes. Crit Rev Biochem Mol Biol 43:289–318.
  • Shroff R, Arbel-Eden A, Pilch D, Ira G, Bonner WM, Petrini JH, Haber JE, and Lichten M. 2004. Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr Biol 14:1703–1711.
  • Sigurdsson S, Van Komen S, Bussen W, Schild D, Albala JS, and Sung P. 2001. Mediator function of the human Rad51B-Rad51C complex in Rad51/RPA-catalyzed DNA strand exchange. Genes Dev 15:3308–3318.
  • Sleeth KM, Sorensen CS, Issaeva N, Dziegielewski J, Bartek J, and Helleday T. 2007. RPA mediates recombination repair during replication stress and is displaced from DNA by checkpoint signalling in human cells. J Mol Biol 373:38–47.
  • Song B, and Sung P. 2000. Functional interactions among yeast Rad51 recombinase, Rad52 mediator, and replication protein A in DNA strand exchange. J Biol Chem 275:15895–15904.
  • Stauffer ME, and Chazin WJ. 2004. Physical interaction between replication protein A and Rad51 promotes exchange on single-stranded DNA. J Biol Chem 279:25638–25645.
  • Stigger E, Drissi R, and Lee SH. 1998. Functional analysis of human replication protein A in nucleotide excision repair. J Biol Chem 273:9337–9343.
  • Stracker TH, Theunissen JW, Morales M, and Petrini JH. 2004. The Mre11 complex and the metabolism of chromosome breaks: the importance of communicating and holding things together. DNA Repair (Amst) 3:845–854.
  • Sugiyama T, and Kowalczykowski SC. 2002. Rad52 protein associates with replication protein A (RPA)-single-stranded DNA to accelerate Rad51-mediated displacement of RPA and presynaptic complex formation. J Biol Chem 277:31663–31672.
  • Sugiyama T, Zaitseva EM, and Kowalczykowski SC. 1997. A single-stranded DNA-binding protein is needed for efficient presynaptic complex formation by the Saccharomyces cerevisiae Rad51 protein. J Biol Chem 272:7940–7945.
  • Sung P. 1997a. Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. J Biol Chem 272:28194–28197.
  • Sung P. 1997b. Yeast Rad55 and Rad57 proteins form a heterodimer that functions with replication protein A to promote DNA strand exchange by Rad51 recombinase. Genes Dev 11:1111–1121.
  • Symington LS. 2002. Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair. Microbiol Mol Biol Rev 66:630–670, table of contents.
  • Tiranti V, Rocchi M, DiDonato S, and Zeviani M. 1993. Cloning of human and rat cDNAs encoding the mitochondrial single-stranded DNA-binding protein (SSB). Gene 126:219–225.
  • Tsurimoto T, Fairman MP, and Stillman B. 1989. Simian virus 40 DNA replication in vitro: identification of multiple stages of initiation. Mol Cell Biol 9:3839–3849.
  • Vassin VM, Wold MS, and Borowiec JA. 2004. Replication protein A (RPA) phosphorylation prevents RPA association with replication centers. Mol Cell Biol 24:1930–1943.
  • Volker M, Mone MJ, Karmakar P, van Hoffen A, Schul W, Vermeulen W, Hoeijmakers JH, van Driel R, van Zeeland AA, and Mullenders LH. 2001. Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell 8:213–224.
  • Wadsworth RI, and White MF. 2001. Identification and properties of the crenarchaeal single-stranded DNA binding protein from Sulfolobus solfataricus. Nucleic Acids Res 29:914–920.
  • Waga S, and Stillman B. 1998. The DNA replication fork in eukaryotic cells. Annu Rev Biochem 67:721–751.
  • Walter J, and Newport JW. 1997. Regulation of replicon size in Xenopus egg extracts. Science 275:993–995.
  • Walter J, and Newport J. 2000. Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha. Mol Cell 5:617–627.
  • Wang H, Guan J, Wang H, Perrault AR, Wang Y, and Iliakis G. 2001. Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia-mutated and DNA-dependent protein kinase. Cancer Res 61:8554–8563.
  • Wang LC, Stone S, Hoatlin ME, and Gautier J. 2008. Fanconi anemia proteins stabilize replication forks. DNA Repair (Amst) 7:1973–1981.
  • Williams RS, Moncalian G, Williams JS, Yamada Y, Limbo O, Shin DS, Groocock LM, Cahill D, Hitomi C, Guenther G, Moiani D, Carney JP, Russell P, and Tainer J. 2008. Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell 135:97–109.
  • Wobbe CR, Weissbach L, Borowiec JA, Dean FB, Murakami Y, Bullock P, and Hurwitz J. 1987. Replication of simian virus 40 origin-containing DNA in vitro with purified proteins. Proc Natl Acad Sci USA 84:1834–1838.
  • Wold MS. 1997. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu Rev Biochem 66:61–92.
  • Wold MS, and Kelly T. 1988. Purification and characterization of replication protein A, a cellular protein required for in vitro replication of simian virus 40 DNA. Proc Natl Acad Sci USA 85:2523–2527.
  • Wold MS, Weinberg DH, Virshup DM, Li JJ, and Kelly TJ. 1989. Identification of cellular proteins required for simian virus 40 DNA replication. J Biol Chem 264:2801–2809.
  • Wong AK, Pero R, Ormonde PA, Tavtigian SV, and Bartel PL. 1997. RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J Biol Chem 272:31941–1944.
  • Wong JM, Ionescu D, and Ingles CJ. 2003. Interaction between BRCA2 and replication protein A is compromised by a cancer- predisposing mutation in BRCA2. Oncogene 22:28–33.
  • Wu L. 2008. Wrestling off RAD51: a novel role for RecQ helicases. Bioessays 30:291–295.
  • Wyka IM, Dhar K, Binz SK, and Wold MS. 2003. Replication protein A interactions with DNA: differential binding of the core domains and analysis of the DNA interaction surface. Biochemistry 42:12909–12918.
  • Yan H, and Newport J. 1995. An analysis of the regulation of DNA synthesis by cdk2, Cip1, and licensing factor. J Cell Biol 129:1–15.
  • Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH, Zheng N, Chen PL, Lee WH, and Pavletich NP. 2002. BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science 297:1837–1848.
  • Yang W. 2003. Damage repair DNA polymerases Y. Curr Opin Struct Biol 13:23–30.
  • Yodh JG, Stevens BC, Kanagaraj R, Janscak P, and Ha T. 2009. BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation. Embo J 28:405–416.
  • Yuan SS, Lee SY, Chen G, Song M, Tomlinson GE, and Lee EY. 1999. BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. Cancer Res 59:3547–3551.
  • Zernik-Kobak M, Vasunia K, Connelly M, Anderson CW, and Dixon K. 1997. Sites of UV-induced phosphorylation of the p34 subunit of replication protein A from HeLa cells. J Biol Chem 272:23896–23904.
  • Zhou BB, and Elledge SJ. 2000. The DNA damage response: putting checkpoints in perspective. Nature 408:433–439.
  • Zou L, and Elledge SJ. 2003. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300:1542–1548.
  • Zou L, Liu D, and Elledge SJ. 2003. Replication protein A-mediated recruitment and activation of Rad17 complexes. Proc Natl Acad Sci USA 100:13827–13832.

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