Affordable Access

Publisher Website

MYC impairs resolution of site-specific DNA double-strand breaks repair.

Authors
Type
Published Article
Journal
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
0027-5107
Publisher
Elsevier
Publication Date
Volume
774
Pages
6–13
Identifiers
DOI: 10.1016/j.mrfmmm.2015.02.005
PMID: 25770827
Source
Medline
Keywords
  • Asisi Restriction Enzyme
  • Dsb Repair
  • Myc
  • Mycn
  • Site-Specific Dsbs

Abstract

Although it is established that when overexpressed, the MYC family proteins can cause DNA double-stand 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 γH2AX 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.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments
F