DNA Damage Response Factors from Diverse Pathways, Including DNA Crosslink Repair, Mediate Alternative End Joining

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Alternative EJ (Alt-EJ) is a chromosomal double strand break (DSB) repair pathway that often uses short stretches of homology (microhomology) to bridge the break during repair. Alt-EJ involves bypass of the classical non-homologous end joining (c-NHEJ) pathway, and hence may be important for DSBs that are not readily repaired by c-NHEJ, such as DSBs requiring extensive end processing prior to ligation. Since the factors that mediate Alt-EJ are unclear, we identified DNA damage response factors that differentially promote Alt-EJ relative to an EJ event that is a composite of c-NHEJ and Alt-EJ. Several of these factors promote other repair events that are enhanced by loss of c-NHEJ, namely homologous recombination (HR), including DNA crosslink repair factors, such as FANCA. We then investigated distinctions among individual factors. For instance, we found that loss of c-NHEJ appears to diminish the influence of FANCA on Alt-EJ, but enhances the effect of PARP inhibition. Furthermore, we find that FANCA and DNA2 differentially affect another aspect of the DNA damage response, namely end resection. Based on these findings, we suggest that several aspects of the DNA damage response are important for Alt-EJ.

Vyšlo v časopise: DNA Damage Response Factors from Diverse Pathways, Including DNA Crosslink Repair, Mediate Alternative End Joining. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004943
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004943

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