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Special Report

DNA double-strand break repair, immunodeficiency and the RIDDLE syndrome

&
Pages 169-185 | Published online: 10 Jan 2014

References

  • Hopfner KP, Craig L, Moncalian G et al. The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. Nature418(6897), 562–566 (2002).
  • Williams RS, Moncalian G, Williams JS et al. Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell135(1), 97–109 (2008).
  • Uziel T, Lerenthal Y, Moyal L et al. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J.22, 5612–5621 (2003).
  • Burma S, Chen BP, Murphy M et al. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem.276, 42462–42467 (2001).
  • Stucki M, Clapperton JA, Mohammad D et al. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell123, 1213–1226 (2005).
  • Stewart GS, Wang B, Bignell CR et al. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature421, 961–966 (2003).
  • Lukas C, Melander F, Stucki M et al. MDC1 couples DNA double-strand break recognition by NBN with its H2AX-dependent chromatin retention. EMBO J.23, 2674–2683 (2004).
  • Huen MS, Grant R, Manke I et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell131, 901–914 (2007).
  • Kolas NK, Chapman JR, Nakada S et al. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science318, 1637–1640 (2007).
  • Mailand N, Bekker-Jensen S, Faustrup H et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell131, 887–900 (2007).
  • Kim H, Chen J, Yu X. Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science316, 1202–1205 (2007).
  • Sobhian B, Shao G, Lilli DR et al. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science316, 1198–1202 (2007).
  • Wang B, Matsuoka S, Ballif BA et al. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science316, 1194–1198 (2007).
  • Feng L, Huang J, Chen J. MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev.23(6), 719–728 (2009).
  • Shao G, Patterson-Fortin J, Messick TE et al. MERIT40 controls BRCA1–Rap80 complex integrity and recruitment to DNA double-strand breaks. Genes Dev.23(6), 740–754 (2009).
  • Wang B, Hurov K, Hofmann K, Elledge SJ. NBA1, a new player in the BRCA1 A complex, is required for DNA damage resistance and checkpoint control. Genes Dev.23(6), 729–739 (2009).
  • Shao G, Lilli DR, Patterson-Fortin J et al. The Rap80–BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proc. Natl Acad. Sci. USA106(9), 3166–3171 (2009).
  • Polanowska J, Martin JS, Garcia-Muse T et al. A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage sites. EMBO J.25, 2178–2188 (2006).
  • Botuyan MV, Lee J, Ward IM et al. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell127(7), 1361–1373 (2006).
  • Schotta G, Sengupta R, Kubicek S et al. A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse. Genes Dev.22(15), 2048–2061 (2008).
  • DiTullio RA Jr, Mochan TA, Venere M et al. 53BP1 functions in an ATM-dependent checkpoint pathway that is constitutively activated in human cancer. Nat. Cell. Biol.4, 998–1002 (2004).
  • Difilippantonio S, Gapud E, Wong N et al. 53BP1 facilitates long-range DNA end-joining during V(D)J recombination. Nature456, 529–533 (2008).
  • Bunting SF, Callén E, Wong N et al. 53BP1 inhibits homologous recombination in BRAC1-deficient cells by blocking resection of DNA breaks. Cell141(2), 243–254 (2010).
  • Yata K, Esashi F. Dual role of Cdks in DNA repair: to be, or not to be. DNA repair (Amst).8(1), 6–18 (2009).
  • Huertas P. DNA resection in eukaryotes: deciding how to fix the break. Nat. Struct. Mol. Biol.17(1), 11–16 (2010).
  • Sartori AA, Lukas C, Coates J et al. Human CtIP promotes DNA end resection. Nature450(7169), 509–514 (2007).
  • Huertas P, Jackson SP. Human CtIP mediates cell cycle control of DNA end resection and double strand break repair. J. Biol. Chem.284(14), 9558–9565 (2009).
  • Chen L, Nievera CJ, Lee AY, Wu X. Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair. J. Biol. Chem.283(12), 7713–7720 (2008).
  • Yun MH, Hiom K. CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle. Nature459(7245), 460–463 (2009).
  • Bouwman P, Aly A, Escandell JM et al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat. Struct. Mol. Biol.17(6), 688–695 (2010).
  • Cao L, Xu X, Bunting SF et al. A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. Mol. Cell35(4), 534–541 (2009).
  • Gravel S, Chapman JR, Magill C, Jackson SP. DNA helicases Sgs1 and BLM promote DNA double-strand break resection. Genes Dev.22(20), 2767–2772 (2008).
  • Nimonkar AV, Ozsoy AZ, Genschel J et al. Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc. Natl Acad. Sci. USA105(44), 16906–16911 (2008).
  • Wyman C, Kanaar R. DNA double-strand break repair: all’s well that ends well. Annu. Rev. Genet.40, 363–383 (2006).
  • Mimitou EP, Symington LS. Nucleases and helicases take center stage in homologous recombination. Trends Biochem. Sci.34(5), 264–272 (2009).
  • Muñoz IM, Hain K, Déclais A-C et al. Coordination of structure-specific nucleases by human SLX4/BTB12 is required for DNA repair. Mol. Cell35, 116–127 (2009).
  • Klein H, Symington L. Breaking up just got easier to do. Cell138(1), 20–22 (2009).
  • Aguilera A, Gómez-González B. Genome instability: a mechanistic view of its causes and consequences. Nat. Rev. Genet.9(3), 204–217 (2008).
  • Kühne M, Riballo E, Rief N et al. A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity. Cancer Res.64(2), 500–508 (2004).
  • Mari PO, Florea BI, Persengiev SP et al. Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4. Proc. Natl Acad. Sci. USA103(49), 18597–18602 (2006).
  • Uematsu N, Weterings E, Yano K et al. Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks. J. Cell. Biol.177(2), 219–229 (2007).
  • Chan DW, Chen BP-C, Prithivirajsingh S et al. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev.16(18), 2333–2338 (2002).
  • Ding Q, Reddy YVR, Wang W et al. Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair. Mol. Cell Biol.23(16), 5836–5848 (2003).
  • Calsou P, Frit P, Humbert O et al. The DNA-dependent protein kinase catalytic activity regulates DNA end processing by means of Ku entry into DNA. J. Biol. Chem.274(12), 7848–7856 (1999).
  • Weterings E, Verkaik NS, Brüggenwirth HT et al. The role of DNA dependent protein kinase in synapsis of DNA ends. Nucleic Acids Res.31(24), 7238–7246 (2003).
  • Meek K, Douglas P, Cui X et al. Trans-autophosphorylation at DNA-dependent protein kinase’s two major autophosphorylation site clusters facilitates end processing but not end joining. Mol. Cell Biol.27(10), 3881–3890 (2007).
  • Mahajan KN, Gangi-Peterson L, Sorscher DH et al. Association of terminal deoxynucleotidyl transferase with Ku. Proc. Natl Acad. Sci. USA96(24), 13926–13931 (1999).
  • Mahajan KN, McElhinny SAN, Mitchell BS, Ramsden DA. Association of DNA polymerase µ (pol µ) with Ku and ligase IV: role for pol µ in end-joining double-strand break repair. Mol. Cell Biol.22(14), 5194–5202 (2002).
  • Ma Y, Pannicke U, Schwarz K, Lieber MR. Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in non-homologous end joining and V(D)J recombination. Cell108(6), 781–794 (2002).
  • Gu J, Lu H, Tsai AG et al. Single-stranded DNA ligation and XLF-stimulated incompatible DNA end ligation by the XRCC4-DNA ligase IV complex: influence of terminal DNA sequence. Nucleic Acids Res.35(17), 5755–5762 (2007).
  • Tsai CJ, Kim SA, Chu G. Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends. Proc. Natl Acad. Sci. USA104(19), 7851–7856 (2007).
  • Boboila C, Yan C, Wesemann DR et al. Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4. J. Exp. Med.207(2), 417–427 (2010).
  • Boboila C, Jankovic M, Yan CT et al. Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70. Proc. Natl Acad. Sci. USA107(7), 3034–3039 (2010).
  • Simsek D, Jasin M. Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation. Nat. Struct. Mol. Biol.17(4), 410–416 (2010).
  • Bassing CH, Swat W, Alt FW. The mechanism and regulation of chromosomal V(D)J recombination. Cell109(Suppl.), S45–S55 (2002).
  • Jung D, Giallourakis C, Mostoslavsky R, Alt FW. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu. Rev. Immunol.24, 541–570 (2006).
  • Chaudhuri J, Alt FW. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat. Rev. Immunol.4, 541–552 (2004).
  • Franco S, Alt FW, Manis JP. Pathways that suppress programmed DNA breaks from progressing to chromosomal breaks and translocations. DNA Repair (Amst).5(9–10), 1030–1041 (2006).
  • Muramatsu M, Kinoshita K, Fagarasan S et al. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell.102(5), 553–563 (2000).
  • Revy P, Muto T, Levy Y et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell102(5), 565–575 (2000).
  • Chaudhuri J, Tian M, Khuong C et al. Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature422(6933), 726–730 (2003).
  • Sohail A, Klapacz J, Samaranayake M et al. Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations. Nucleic Acids Res.31(12), 2990–2994 (2003).
  • Daniel JA, Santos MA, Wang Z et al. PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science329(5994), 914–915 (2010).
  • Chaudhuri J, Alt F. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat. Rev. Immunol.4(7), 541–552 (2004).
  • Lumsden JM, McCarty T, Petiniot LK et al. Immunoglobulin class switch recombination is impaired in ATM-deficient mice. J. Exp. Med.200(9), 1111–1121 (2004).
  • Pan Q, Petit-Frére C, Lähdesmäki A et al. Alternative end joining during switch recombination in patients with ataxia-telangiectasia. Eur. J. Immunol.32(5), 1300–1308 (2002).
  • Reina-San-Martin B, Chen HT, Nussenzweig A, Nussenzweig MC. ATM is required for efficient recombination between immunoglobulin switch regions. J. Exp. Med.200(9), 1103–1110 (2004).
  • Lähdesmäki A, Taylor AM, Chrzanowska KH, Pan-Hammarström Q. Delineation of the role of the Mre11 complex in class switch recombination. J. Biol. Chem.279(16), 16479–16487 (2004).
  • Kracker S, Bergmann Y, Demuth I et al. Nibrin functions in Ig class-switch recombination. Proc. Natl Acad. Sci. USA102(5), 1584–1589 (2005).
  • Reina-San-Martin B, Nussenzweig MC, Nussenzweig A, Difilippantonio S. Genomic instability, endoreduplication, and diminished Ig class-switch recombination in B cells lacking NBN. Proc. Natl Acad. Sci. USA102(5), 1590–1595 (2005).
  • Reina-San-Martin B, Difilippantonio S, Hanitsch L et al. H2AX is required for recombination between immunoglobulin switch regions but not for intra-switch region recombination or somatic hypermutation. J. Exp. Med.197, 1767–1778 (2003).
  • Lou Z, Minter-Dykhouse K, Franco S et al. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol. Cell21, 187–200 (2006).
  • Li L, Halaby MJ, Hakem A et al. RNF8 deficiency impairs class switch recombination, spermatogenesis, and genomic integrity and predisposes for cancer. J. Exp. Med.207(5), 983–997 (2010).
  • Santos MA, Huen MS, Jankovic M et al. Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8. J. Exp. Med.207(5), 973–981 (2010).
  • Manis JP, Morales JC, Xia Z et al. 53BP1 links DNA damage-response pathways to immunoglobulin heavy chain class-switch recombination. Nat. Immunol.5, 481–487 (2004).
  • Ward IM, Reina-San-Martin B, Olaru A et al. 53BP1 is required for class switch recombination. J. Cell Biol.165, 459–464 (2004).
  • Staples ER, McDermott EM, Reiman A et al. Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene. Clin. Exp. Immunol.153(2), 214–220 (2008).
  • Khanna KK, Yan J, Watters D et al. Defective signaling through the B cell antigen receptor in Epstein-Barr virus-transformed ataxia-telangiectasia cells. J. Biol. Chem.272(14), 9489–9495 (1997).
  • Giovannetti A, Mazzetta F, Caprini E et al. Skewed T-cell receptor repertoire, decreased thymic output, and predominance of terminally differentiated T cells in ataxia telangiectasia. Blood100(12), 4082–4089 (2002).
  • Vacchio MS, Olaru A, Livak F, Hodes RJ. ATM deficiency impairs thymocyte maturation because of defective resolution of T cell receptor α locus coding end breaks. Proc. Natl Acad. Sci. USA104(15), 6323–6328 (2008).
  • Bredemeyer AL, Sharma GG, Huang CY et al. ATM stabilizes DNA double-strand-break complexes during V(D)J recombination. Nature442, 466–470 (2006).
  • Aurias A, Dutrillaux B, Buriot D, Lejeune J. High frequencies of inversions and translocations of chromosomes 7 and 14 in ataxia telangiectasia. Mutat. Res.69(2), 369–374 (1980).
  • Mahowald GK, Baron JM, Mahowald MA et al. Aberrantly resolved RAG-mediated DNA breaks in ATM-deficient lymphocytes target chromosomal breakpoints in cis. Proc. Natl Acad. Sci. USA106(43), 18339–18344 (2009).
  • Carney JP, Maser RS, Olivares H et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell93(3), 477–486 (1998).
  • Varon R, Vissinga C, Platzer M et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell93(3), 467–476 (1998).
  • Weemaes CM, Smeets DF, van der Burgt CJ. Nijmegen Breakage syndrome: a progress report. Int. J. Radiat. Biol.66(Suppl. 6), S185–S188 (1994).
  • Chrzanowska KH, Kleijer WJ, Krajewska-Walasek M et al. Eleven Polish patients with microcephaly, immunodeficiency, and chromosomal instability: the Nijmegen breakage syndrome. Am. J. Med. Genet.57(3), 462–471 (1995).
  • Gregorek H, Chrzanowska KH, Michałkiewicz J et al. Heterogeneity of humoral immune abnormalities in children with Nijmegen breakage syndrome: an 8-year follow-up study in a single centre. Clin. Exp. Immunol.130(2), 319–324 (2002).
  • Digweed M, Sperling K. Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks. DNA Repair (Amst).3(8–9), 1207–1217 (2004).
  • Deriano L, Stracker TH, Baker A et al. Roles for NBN in alternative nonhomologous end-joining of V(D)J recombination intermediates. Mol. Cell34(1), 13–25 (2009).
  • Helmink BA, Bredemeyer AL, Lee BS et al. MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks. J. Exp. Med.206(3), 669–679 (2009).
  • Stewart GS, Maser RS, Stankovic T et al. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell99(6), 577–587 (1999).
  • Delia D, Piane M, Buscemi G et al. MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder. Hum. Mol. Genet.13(18), 2155–2163 (2004).
  • Fernet M, Gribaa M, Salih MA et al. Identification and functional consequences of a novel MRE11 mutation affecting 10 Saudi Arabian patients with the ataxia telangiectasia-like disorder. Hum. Mol. Genet.14(2), 307–318 (2005).
  • Waltes R, Kalb R, Gatei M et al. Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder. Am. J. Hum. Genet.84(5), 605–616 (2009).
  • Shull ER, Lee Y, Nakane H et al. Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS. Genes Dev.23(2), 171–180 (2009).
  • Warcoin M, Lespinasse J, Despouy G et al. Fertility defects revealing germline biallelic nonsense NBN mutations. Hum. Mutat.30(3), 424–430 (2009).
  • Riballo E, Critchlow SE, Teo SH et al. Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient. Curr. Biol.9(13), 699–702 (1999).
  • O’Driscoll M, Cerosaletti KM, Girard PM et al. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol. Cell8(6), 1175–1185 (2001).
  • Ben-Omran TI, Cerosaletti K, Concannon P et al. A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome. Am. J. Med. Genet. A.137A(3), 283–287 (2005).
  • Buck D, Moshous D, de Chasseval R et al. Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV. Eur. J. Immunol.36(1), 224–235 (2006).
  • Enders A, Fisch P, Schwarz K et al. A severe form of human combined immunodeficiency due to mutations in DNA ligase IV. J. Immunol.176(8), 5060–5068 (2006).
  • van der Burg M, van Veelen LR, Verkaik NS et al. A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation. J. Clin. Invest.116(1), 137–145 (2006).
  • Toita N, Hatano N, Ono S et al. Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome. Am. J. Med. Genet. A.143(7), 742–745 (2007).
  • Pan-Hammarström Q, Jones AM, Lähdesmäki A et al. Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells. J. Exp. Med.201(2), 189–194 (2005).
  • Moshous D, Callebaut I, de Chasseval R et al. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell105(2), 177–186 (2001).
  • Li L, Moshous D, Zhou Y et al. A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans. J. Immunol.168(12), 6323–6329 (2002).
  • Kobayashi N, Agematsu K, Sugita K et al. Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families. Hum. Genet.112(4), 348–352 (2003).
  • Moshous D, Pannetier C, Chasseval Rd R et al. Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. J. Clin. Invest.111(3), 381–387 (2003).
  • Noordzij JG, Verkaik NS, van der Burg M et al. Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow. Blood101(4), 1446–1452 (2003).
  • Ege M, Ma Y, Manfras B et al. Omenn syndrome due to ARTEMIS mutations. Blood.105(11), 4179–4186 (2005).
  • Pannicke U, Hönig M, Schulze I, et al. The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. Hum. Mutat.31(2), 197–207 (2010).
  • Ahnesorg P, Smith P, Jackson SP. LF interacts with the XRCC4–DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell124(2), 301–313 (2006).
  • Buck D, Malivert L, de Chasseval R et al. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell124(2), 287–299 (2006).
  • Dutrannoy V, Demuth I, Baumann U et al. Clinical variability and novel mutations in the NHEJ1 gene in patients with a Nijmegen breakage syndrome-like phenotype. Hum. Mutat.31(9), 1059–1068 (2010).
  • Rooney S, Sekiguchi J, Zhu C et al. Leaky SCID phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice. Mol. Cell10(6), 1379–1390 (2002).
  • Rooney S, Alt FW, Lombard D et al. Defective DNA repair and increased genomic instability in Artemis-deficient murine cells. J. Exp. Med.197(5), 553–565 (2003).
  • Du L, van der Burg M, Popov SW et al. Involvement of Artemis in nonhomologous end-joining during immunoglobulin class switch recombination. J. Exp. Med.205(13), 3031–3040 (2008).
  • Blunt T, Finnie NJ, Taccioli GE et al. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine SCID mutation. Cell80(5), 813–823 (1995).
  • Shin EK, Perryman LE, Meek K. A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation. J. Immunol.158(8), 3565–3569 (1997).
  • van der Burg M, Ijspeert H, Verkaik NS et al. A DNA-PKCS mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining. J. Clin. Invest.119(1), 91–98 (2009).
  • Nussenzweig A, Chen C, da Costa Soares V et al. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature382(6591), 551–555 (1996).
  • Gu Y, Seidl KJ, Rathbun GA et al. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity7(5), 653–665 (1997).
  • Li G, Nelsen C, Hendrickson EA. Ku86 is essential in human somatic cells. Proc. Natl Acad. Sci. USA99(2), 832–837 (2002).
  • Stewart GS, Stankovic T, Byrd PJ et al. RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling. Proc. Natl Acad. Sci. USA104, 16910–16915 (2007).
  • Stewart GS, Panier S, Townsend K et al. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell136, 420–434 (2009).
  • Penengo L, Mapelli M, Murachelli AG et al. Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin. Cell124, 1183–1195 (2006).
  • Doil C, Mailand N, Bekker-Jensen S et al. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell136, 435–446 (2009).
  • Bekker-Jensen S, Rendtlew Danielsen J, Fugger K et al. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat. Cell. Biol.12(1), 80–86 (2010).
  • Boulton SJ. DNA repair: Decision at the break point. Nature465(7296), 301–302 (2010).
  • Bothmer A, Robbiani DF, Feldhahn N et al. 53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination. J. Exp. Med.207(4), 855–865 (2010).
  • Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat. Rev. Mol. Cell Biol.9(10), 759–769 (2008).
  • Laine A, Topisirovic I, Zhai D et al. Regulation of p53 localization and activity by Ubc13. Mol. Cell Biol.26(23), 8901–8913 (2006).
  • Topisirovic I, Gutierrez GJ, Chen M et al. Control of p53 multimerization by Ubc13 is JNK-regulated. Proc. Natl Acad. Sci. USA106(31), 12676–12681 (2009).
  • Laribee RN, Fuchs SM, Strahl BD. H2B ubiquitylation in transcriptional control: a FACT-finding mission. Genes Dev.21(7), 737–743 (2007).
  • Weake VM, Workman JL. Histone ubiquitination: triggering gene activity. Mol. Cell29(6), 653–663 (2008).
  • Wang H, Wang L, Erdjument-Bromage H et al. Role of histone H2A ubiquitination in Polycomb silencing. Nature431(7010), 873–878 (2004).
  • Cao R, Tsukada Y, Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol. Cell20(6), 845–854 (2005).
  • Zhou W, Zhu P, Wang J et al. Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation. Mol. Cell29(1), 69–80 (2008).
  • Wu J, Huen MS, Lu LY et al. Histone ubiquitination associates with BRCA1-dependent DNA damage response. Mol. Cell Biol.29(3), 849–860 (2009).

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