期刊
DNA REPAIR
卷 88, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.dnarep.2020.102807
关键词
Drosophila xrcc2; Mitotic DNA damage repair; Rad51 paralog; CRISPR/Cas9; Genotoxic stress
资金
- Deutsche Forschungsgemeinschaft DFG [NA 427/4-1]
- University of Hohenheim
Genomic integrity is challenged by endo- and exogenous assaults that are combated by highly conserved DNA repair mechanisms. Repair of DNA double-strand breaks (DSBs) is of particular importance, as DSBs inflict chromosome breaks that are the basis of genomic instability. High fidelity recombination repair of DSBs relies on the Rad51 recombinase, aided by several Rad51 paralogs. Despite their significant contribution to DSB repair, the individual roles for Rad51 paralogs are incompletely understood. Drosophila serves as a metazoan model for DNA damage repair at the organismal level. Yet, only two out of four Rad51 paralogs have been studied so far and both are restricted to meiotic recombination repair. Using CRISPR/Cas9 technology, we have generated the first X-ray repair cross complementing 2 (xrcc2) null mutant in Drosophila. Like any other Drosophila Rad51 homologue, loss of xrcc2 does not affect fly development. We found that Drosophila xrcc2 - despite a specific expression in ovaries - is not essential for meiotic DSB repair, but supports the process. In contrast, xrcc2 is required for mitotic DNA damage repair: the mutants are highly sensitive towards various genotoxic stressors, including ionizing radiation, which significantly increase mortality. Moreover, loss of xrcc2 provokes chromosome aberrations in mitotic larval neuroblasts under unstressed conditions and enduring chromosomal breaks as well as persistent repair foci after irradiation exposure. Together these results demonstrate that xrcc2 plays a crucial role in combating genotoxic insult by controlling DSB repair in somatic cells of Drosophila.
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