CST/Polα/primase-mediated fill-in synthesis at DSBs

References

• Stinson BM, Loparo JJ. Repair of DNA double-strand breaks by the nonhomologous end joining pathway. Annu Rev Biochem. 2021;90:137–164.
   PubMed Web of Science ®Google Scholar
• Wright WD, Shah SS, Heyer WD. Homologous recombination and the repair of DNA double-strand breaks. J Biol Chem. 2018;293:10524–10535.
   PubMed Web of Science ®Google Scholar
• Bhargava R, Onyango DO, Stark JM. Regulation of single-strand annealing and its role in genome maintenance. Trends Genet. 2016;32:566–575.
   PubMed Web of Science ®Google Scholar
• Mirman Z, de Lange T. 53BP1: a DSB escort. Genes Dev. 2020;34:7–23.
   PubMed Web of Science ®Google Scholar
• Dimitrova N, Chen YC, Spector DL, et al. 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility. Nature. 2008;456:524–528.
   PubMed Web of Science ®Google Scholar
• Lottersberger F, Karssemeijer RA, Dimitrova N, et al. 53BP1 and the LINC complex promote microtubule-dependent DSB mobility and DNA repair. Cell. 2015;163:880–893.
   PubMed Web of Science ®Google Scholar
• Difilippantonio S, Gapud E, Wong N, et al. 53BP1 facilitates long-range DNA end-joining during V(D)J recombination. Nature. 2008;456:529–533.
   PubMed Web of Science ®Google Scholar
• Mirman Z, Lottersberger F, Takai H, et al. 53BP1-RIF1-Shieldin counteracts DSB resection through CST- and Polα-dependent fill-in. Nature. 2018;560:112–116.
   PubMed Web of Science ®Google Scholar
• Escribano-Díaz C, Orthwein A, Fradet-Turcotte A, et al. A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol Cell. 2013;49:872–883.
   PubMed Web of Science ®Google Scholar
• Zimmermann M, Lottersberger F, Buonomo SB, et al. 53BP1 regulates DSB repair using Rif1 to control 5’ end resection. Science. 2013;339:700–704.
   PubMed Web of Science ®Google Scholar
• Di Virgilio M, Callen E, Yamane A, et al. Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science. 2013;339:711–715.
   PubMed Web of Science ®Google Scholar
• Chapman JR, Barral P, Vannier JB, et al. RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection. Mol Cell. 2013;49:858–871.
   PubMed Web of Science ®Google Scholar
• Boersma V, Moatti N, Segura-Bayona S, et al. MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5’ end resection. Nature. 2015;521:537–540.
   PubMed Web of Science ®Google Scholar
• Xu G, Chapman JR, Brandsma I, et al. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature. 2015;521:541–544.
   PubMed Web of Science ®Google Scholar
• Dev H, Chiang TW, Lescale C, et al. Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells. Nat Cell Biol. 2018;20:954–965.
   PubMed Web of Science ®Google Scholar
• Ghezraoui H, Oliveira C, Becker JR, et al. 53BP1 cooperation with the REV7-shieldin complex underpins DNA structure-specific NHEJ. Nature. 2018;560:122–127.
   PubMed Web of Science ®Google Scholar
• Gupta R, Somyajit K, Narita T, et al. DNA repair network analysis reveals shieldin as a key regulator of NHEJ and PARP inhibitor sensitivity. Cell. 2018;173:972–988.e23.
   PubMed Web of Science ®Google Scholar
• Noordermeer SM, Adam S, Setiaputra D, et al. The shieldin complex mediates 53BP1-dependent DNA repair. Nature. 2018;560:117–121.
   PubMed Web of Science ®Google Scholar
• de Lange T. Shelterin-Mediated telomere protection. Annu Rev Genet. 2018;52:223–247.
   PubMed Web of Science ®Google Scholar
• Zhao F, Kim W, Gao H, et al. ASTE1 promotes shieldin-complex-mediated DNA repair by attenuating end resection. Nat Cell Biol. 2021;23:894–904.
   PubMed Web of Science ®Google Scholar
• Setiaputra D, Durocher D. Shieldin - the protector of DNA ends. EMBO Rep. 2019;20:5.
   Web of Science ®Google Scholar
• Goulian M, Heard CJ, Grimm SL. Purification and properties of an accessory protein for DNA polymerase alpha/primase. J Biol Chem. 1990;265:13221–13230.
   PubMed Web of Science ®Google Scholar
• Goulian M, Heard CJ. The mechanism of action of an accessory protein for DNA polymerase alpha/primase. J Biol Chem. 1990;265:13231–13239.
   PubMed Web of Science ®Google Scholar
• Gao H, Cervantes RB, Mandell EK, et al. RPA-Like proteins mediate yeast telomere function. Nat Struct Mol Biol. 2007;14:208–214.
   PubMed Web of Science ®Google Scholar
• Lim CJ, Barbour AT, Zaug AJ, et al. The structure of human CST reveals a decameric assembly bound to telomeric DNA. Science. 2020;368:1081–1085.
   PubMed Web of Science ®Google Scholar
• Bhattacharjee A, Wang Y, Diao J, et al. Dynamic DNA binding, junction recognition and G4 melting activity underlie the telomeric and genome-wide roles of human CST. Nucleic Acids Res. 2017;45:12311–12324.
   PubMed Web of Science ®Google Scholar
• Hom RA, Wuttke DS. Human CST prefers G-rich but not necessarily telomeric sequences. Biochemistry. 2017;56:4210–4218.
   PubMed Web of Science ®Google Scholar
• Miyake Y, Nakamura M, Nabetani A, et al. RPA-Like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol Cell. 2009;36:193–206.
   PubMed Web of Science ®Google Scholar
• Stewart JA, Wang F, Chaiken MF, et al. Human CST promotes telomere duplex replication and general replication restart after fork stalling. Embo J. 2012;31:3537–3549.
   PubMed Web of Science ®Google Scholar
• Chastain M, Zhou Q, Shiva O, et al. Human CST Facilitates genome-wide RAD51 recruitment to GC-rich repetitive sequences in response to replication stress. Cell Rep. 2016;16:1300–1314.
   PubMed Web of Science ®Google Scholar
• Zhang M, Wang B, Li T, et al. Mammalian CST averts replication failure by preventing G-quadruplex accumulation. Nucleic Acids Res. 2019;47:5243–5259.
   PubMed Web of Science ®Google Scholar
• Chen LY, Redon S, Lingner J. The human CST complex is a terminator of telomerase activity. Nature. 2012;488:540–544.
   PubMed Web of Science ®Google Scholar
• Lue NF. Evolving linear chromosomes and telomeres: a C-strand-centric view. Trends Biochem Sci. 2018;43:314–326.
   PubMed Web of Science ®Google Scholar
• Wu P, Takai H, de Lange T. Telomeric 3’ overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST. Cell. 2012;150:39–52.
   PubMed Web of Science ®Google Scholar
• Gu P, Min JN, Wang Y, et al. CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion. Embo J. 2012;31:2309–2321.
   PubMed Web of Science ®Google Scholar
• Wang F, Stewart JA, Kasbek C, et al. Human CST has independent functions during telomere duplex replication and C-strand fill-in. Cell Rep. 2012;2:1096–1103.
   PubMed Web of Science ®Google Scholar
• Chen LY, Majerská J, Lingner J. Molecular basis of telomere syndrome caused by CTC1 mutations. Genes Dev. 2013;27:2099–2108.
   PubMed Web of Science ®Google Scholar
• Takai H, Jenkinson E, Kabir S, et al. A POT1 mutation implicates defective telomere end fill-in and telomere truncations in coats plus. Genes Dev. 2016;30:812–826.
   PubMed Web of Science ®Google Scholar
• Feng X, Hsu SJ, Kasbek C, et al. CTC1-Mediated C-strand fill-in is an essential step in telomere length maintenance. Nucleic Acids Res. 2017;45:4281–4293.
   PubMed Web of Science ®Google Scholar
• Gu P, Jia S, Takasugi T, et al. CTC1-STN1 coordinates G- and C-strand synthesis to regulate telomere length. Aging Cell. 2018;17:e12783.
   PubMed Web of Science ®Google Scholar
• Wan M, Qin J, Songyang Z, et al. OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1, associates with TPP1 and is implicated in telomere length regulation. J Biol Chem. 2009;284:26725–26731.
   PubMed Web of Science ®Google Scholar
• Pinzaru AM, Hom RA, Beal A, et al. Telomere replication stress induced by POT1 inactivation accelerates tumorigenesis. Cell Rep. 2016;15:2170–2184.
   PubMed Web of Science ®Google Scholar
• Hockemeyer D, Daniels JP, Takai H, et al. Recent expansion of the telomeric complex in rodents: two distinct POT1 proteins protect mouse telomeres. Cell. 2006;126:63–77.
   PubMed Web of Science ®Google Scholar
• Hockemeyer D, Palm W, Wang RC, et al. Engineered telomere degradation models dyskeratosis congenita. Genes Dev. 2008;22:1773–1785.
   PubMed Web of Science ®Google Scholar
• Hockemeyer D, Palm W, Else T, et al. Telomere protection by mammalian Pot1 requires interaction with Tpp1. Nat Struct Mol Biol. 2007;14:754–761.
   PubMed Web of Science ®Google Scholar
• Kibe T, Osawa GA, Keegan CE, et al. Telomere protection by TPP1 is mediated by POT1a and POT1b. Mol Cell Biol. 2010;30:1059–1066.
   PubMed Web of Science ®Google Scholar
• Kibe T, Zimmermann M, de Lange T. TPP1 blocks an ATR-mediated resection mechanism at telomeres. Mol Cell. 2016;61:236–246.
   PubMed Web of Science ®Google Scholar
• Cai SW, Zinder JC, Svetlov V, et al. Cryo-EM structure of the human CST–Polα/primase complex in a recruitment state. Nat Struct Mol Biol. 2022;29:813–819.
   PubMed Web of Science ®Google Scholar
• He Q, Lin X, Chavez BL, et al. Structures of the human CST-Polα-primase complex bound to telomere templates. Nature. 2022;608(7924).
   Web of Science ®Google Scholar
• Anderson BH, Kasher PR, Mayer J, et al. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet. 2012;44:338–342.
   PubMed Web of Science ®Google Scholar
• Simon AJ, Lev A, Zhang Y, et al. Mutations in STN1 cause coats plus syndrome and are associated with genomic and telomere defects. J Exp Med. 2016;213:1429–1440.
   PubMed Web of Science ®Google Scholar
• Passi GR, Shamim U, Rathore S, et al. An Indian child with coats plus syndrome due to mutations in STN1. Am J Med Genet a. 2020;182:2139–2144.
   PubMed Web of Science ®Google Scholar
• Jumper J, Evans R, Pritzel A, et al. Applying and improving AlphaFold at CASP14. Proteins. 2021;89:1711–1721.
   PubMed Web of Science ®Google Scholar
• Varadi M, Anyango S, Deshpande M, et al. AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 2021;50(D1):D439–D444.
   Web of Science ®Google Scholar
• Mirman Z, Sasi NK, King A, et al. 53BP1-Shieldin-Dependent DSB processing in BRCA1-deficient cells requires CST-Polα-primase fill-in synthesis. Nat Cell Biol. 2022;24:51–61.
   PubMed Web of Science ®Google Scholar
• Ochs F, Somyajit K, Altmeyer M, et al. 53BP1 fosters fidelity of homology-directed DNA repair. Nat Struct Mol Biol. 2016;23:714–721.
   PubMed Web of Science ®Google Scholar
• Zaug AJ, Goodrich KJ, Song JJ, et al. Reconstitution of a telomeric replicon organized by CST. Nature 2022;
   PubMed Web of Science ®Google Scholar
• Canela A, Sridharan S, Sciascia N, et al. DNA breaks and end resection measured genome-wide by end sequencing. Mol Cell. 2016;63:898–911.
   PubMed Web of Science ®Google Scholar
• Wu W, Hill SE, Nathan WJ, et al. Neuronal enhancers are hotspots for DNA single-strand break repair. Nature. 2021;593:440–444.
   PubMed Web of Science ®Google Scholar
• Paiano J, Zolnerowich N, Wu W, et al. Role of 53BP1 in end protection and DNA synthesis at DNA breaks. Genes Dev. 2021;35:1356–1367.
   PubMed Web of Science ®Google Scholar
• Schimmel J, Muñoz-Subirana N, Kool H, et al. Small tandem DNA duplications result from CST-guided Pol α-primase action at DNA break termini. Nat Commun. 2021;12:4843.
   PubMed Web of Science ®Google Scholar
• Kuchta RD, Stengel G. Mechanism and evolution of DNA primases. Biochim Biophys Acta. 2010;1804:1180–1189.
   PubMed Web of Science ®Google Scholar
• Evans R, O’Neill M, Pritzel A, et al. Protein complex prediction with Alphafold-multimer. bioRxiv. 2021
   Google Scholar
• Liang L, Feng J, Zuo P, et al. Molecular basis for assembly of the shieldin complex and its implications for NHEJ. Nat Commun. 2020;11:1972.
   PubMed Web of Science ®Google Scholar
• Pettersen EF, Goddard TD, Huang CC, et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 2021;30:70–82.
   PubMed Web of Science ®Google Scholar
• Barazas M, Annunziato S, Pettitt SJ, et al. The CST complex mediates end protection at double-strand breaks and promotes PARP inhibitor sensitivity in BRCA1-deficient cells. Cell Rep. 2018;23:2107–2118.
   PubMed Web of Science ®Google Scholar
• Chaudhuri J, Alt FW. Class-Switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat Rev Immunol. 2004;4:541–552.
   PubMed Web of Science ®Google Scholar
• Hanzlikova H, Kalasova I, Demin AA, et al. The importance of poly(ADP-ribose) polymerase as a sensor of unligated okazaki fragments during DNA replication. Mol Cell. 2018;71:319–331.e3.
   PubMed Web of Science ®Google Scholar