Jackson, S. P. & Bartek, J. The DNA-damage response in human biology and disease. Nature 461, 1071–1078 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Futreal, P. A. et al. BRCA1 mutations in primary breast and ovarian carcinomas. Science 266, 120–122 (1994).

Article  CAS  PubMed  Google Scholar 

Silver, D. P. & Livingston, D. M. Mechanisms of BRCA1 tumor suppression. Cancer Discov. 2, 679–684 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005).

Article  CAS  PubMed  Google Scholar 

Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).

Article  CAS  PubMed  Google Scholar 

Pilie, P. G., Gay, C. M., Byers, L. A., O’Connor, M. J. & Yap, T. A. PARP inhibitors: extending benefit beyond BRCA-mutant cancers. Clin. Cancer Res. 25, 3759–3771 (2019).

Article  CAS  PubMed  Google Scholar 

Zlotorynski, E. Shieldin the ends for 53BP1. Nat. Rev. Mol. Cell Biol. 19, 346–347 (2018).

Article  CAS  PubMed  Google Scholar 

Cong, K. et al. Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency. Mol. Cell 81, 3128–3144.e7 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hanzlikova, H. et al. The importance of poly(ADP-ribose) polymerase as a sensor of unligated Okazaki fragments during DNA replication. Mol. Cell 71, 319–331 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cong, K. & Cantor, S. B. Exploiting replication gaps for cancer therapy. Mol. Cell 82, 2363–2369 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simoneau, A., Xiong, R. & Zou, L. The trans cell cycle effects of PARP inhibitors underlie their selectivity toward BRCA1/2-deficient cells. Genes Dev. 35, 1271–1289 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Pommier, Y., O’Connor, M. J. & de Bono, J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci. Transl. Med. 8, 362ps317 (2016).

Article  Google Scholar 

Patel, A. G., Sarkaria, J. N. & Kaufmann, S. H. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc Natl Acad Sci USA 108, 3406–3411 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, F. et al. CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair. Cell Rep. 40, 111297 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bouwman, P. et al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat. Struct. Mol. Biol. 17, 688–695 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zimmermann, M. et al. CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions. Nature 559, 285–289 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

van den Berg, J. et al. A limited number of double-strand DNA breaks is sufficient to delay cell cycle progression. Nucleic Acids Res. 46, 10132–10144 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Tarsounas, M. & Sung, P. The antitumorigenic roles of BRCA1-BARD1 in DNA repair and replication. Nat. Rev. Mol. Cell Biol. 21, 284–299 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rothfuss, A. et al. Induced micronucleus frequencies in peripheral lymphocytes as a screening test for carriers of a BRCA1 mutation in breast cancer families. Cancer Res. 60, 390–394 (2000).

CAS  PubMed  Google Scholar 

Adamo, A. et al. Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. Mol. Cell 39, 25–35 (2010).

Article  CAS  PubMed  Google Scholar 

Lim, K. S. et al. USP1 is required for replication fork protection in BRCA1-deficient tumors. Mol. Cell 72, 925–941 e924 (2018).

Article  CAS  PubMed  Google Scholar 

Du, J. et al. Quantitative assessment of HR and NHEJ activities via CRISPR/Cas9-induced oligodeoxynucleotide-mediated DSB repair. DNA Repair (Amst) 70, 67–71 (2018).

Article  CAS  PubMed  Google Scholar 

Pavani, R. et al. Structure and repair of replication-coupled DNA breaks.Science 385, eadp3867 (2024).

Article  Google Scholar 

Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816–821 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mathew, C. G. Radiolabeling of DNA by nick translation. Methods Mol. Biol. 2, 257–261, (1985).

CAS  PubMed  Google Scholar 

Bunting, S. F. et al. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141, 243–254 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jakobsen, K. P. et al. Minimal resection takes place during break-induced replication repair of collapsed replication forks and is controlled by strand invasion. Cell Rep. 26, 836–844 e833 (2019).

Article  CAS  PubMed  Google Scholar 

Khanna, K. K. & Jackson, S. P. DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet. 27, 247–254 (2001).

Article  CAS  PubMed  Google Scholar 

Davis, L. & Maizels, N. Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair. Proc. Natl Acad. Sci. USA 111, E924–E932 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Polato, F. et al. CtIP-mediated resection is essential for viability and can operate independently of BRCA1. J. Exp. Med. 211, 1027–1036 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar