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Datoteka:Homologous recombinational repair of DNA double-strand damage.jpg

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English: Recombinational repair of DNA double-strand damage - some key steps. ATM (ATM) is a protein kinase that is recruited and activated by DNA double-strand breaks. DNA double-strand damages also activate the Fanconi anemia core complex (FANCA/B/C/E/F/G/L/M).[1] The FA core complex monoubiquitinates the downstream targets FANCD2 and FANCI.[2] ATM activates (phosphorylates) CHEK2 and FANCD2.[3] CHEK2 phosphorylates BRCA1.[4] Ubiquinated FANCD2 complexes with BRCA1 and RAD51.[5] The PALB2 protein acts as a hub,[6] bringing together BRCA1, BRCA2 and RAD51 at the site of a DNA double-strand break, and also binds to RAD51C, a member of the RAD51 paralog complex RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2). The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.[7] RAD51 plays a major role in homologous recombinational repair of DNA during double strand break repair. In this process, an ATP dependent DNA strand exchange takes place in which a single strand invades base-paired strands of homologous DNA molecules. RAD51 is involved in the search for homology and strand pairing stages of the process.
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  1. ↑ (2010). "Susceptibility pathways in Fanconi's anemia and breast cancer". N. Engl. J. Med. 362 (20): 1909–19. DOI:10.1056/NEJMra0809889. PMID 20484397. PMC: 3069698.
  2. ↑ (2009). "The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways". J. Biol. Chem. 284 (38): 25560–8. DOI:10.1074/jbc.M109.007690. PMID 19633289. PMC: 2757957.
  3. ↑ (2011). "Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in response to oxidative damage". DNA Repair (Amst.) 10 (5): 518–25. DOI:10.1016/j.dnarep.2011.02.007. PMID 21466974.
  4. ↑ (2011). "Tumor suppressor CHK2: regulator of DNA damage response and mediator of chromosomal stability". Clin. Cancer Res. 17 (3): 401–5. DOI:10.1158/1078-0432.CCR-10-1215. PMID 21088254.
  5. ↑ (2002). "S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51". Blood 100 (7): 2414–20. DOI:10.1182/blood-2002-01-0278. PMID 12239151.
  6. ↑ (2014). "PALB2: the hub of a network of tumor suppressors involved in DNA damage responses". Biochim. Biophys. Acta 1846 (1): 263–75. DOI:10.1016/j.bbcan.2014.06.003. PMID 24998779. PMC: 4183126.
  7. ↑ (2013). "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway". Mol. Cell. Biol. 33 (2): 387–95. DOI:10.1128/MCB.00465-12. PMID 23149936. PMC: 3554112.

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