期刊
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
卷 774, 期 -, 页码 6-13出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrfmmm.2015.02.005
关键词
Site-specific DSBs; AsiSI restriction enzyme; MYC; MYCN; DSB repair
资金
- P.O.R. Campania FSE Project CREMe
- AIRC [IC 13173]
- MIUR
- Epigenomics Flagship Project - EPIGEN, C.N.R
Although it is established that when overexpressed, the MYC family proteins can cause DNA doublestand breaks (DSBs) and genome instability, the mechanisms involved remain unclear. MYC induced genetic instability may result from increased DNA damage and/or reduced DNA repair. Here we show that when overexpressed, MYC proteins induce a sustained DNA damage response (DDR) and reduce the wave of DSBs repair. We used a cell-based DSBs system whereby, upon induction of an inducible restriction enzyme AsiSI, hundreds of site-specific DSBs are generated across the genome to investigate the role of MYC proteins on DSB. We found that high levels of MYC do not block accumulation of gamma H2AX at AsiSI sites, but delay its clearance, indicating an inefficient repair, while the initial recognition of DNA damage is largely unaffected. Repair of both homologous and nonhomologous repair-prone segments, characterized by high or low levels of recruited RAD51, respectively, was delayed. Collectively, these data indicate that high levels of MYC proteins delay the resolution of DNA lesions engineered to occur in cell cultures. (C) 2015 Elsevier B.V. All rights reserved.
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