Journal
CELL CYCLE
Volume 17, Issue 9, Pages 1138-1145Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2018.1464836
Keywords
Anaphase promoting complex; Cdh1; double-strand breaks; RNF8; NHEJ repair
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Funding
- Chinese National Natural Science Foundation [81773032, 81272488, 81472795, 81602802, 81602680]
- 973 Project [2013CB910300]
- NIH [CA116097, CA122623]
- National Research Foundation of Korea (NRF) - Korean government (MSIP) [NRF-2016R1A6A3A04011000]
- [2013DFB30210]
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Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). The choice between these two pathways is largely influenced by cell cycle phases. HDR can occur only in S/G2 when sister chromatid can provide homologous templates, whereas NHEJ can take place in all phases of the cell cycle except mitosis. Central to NHEJ repair is the Ku70/80 heterodimer which forms a ring structure that binds DSB ends and serves as a platform to recruit factors involved in NHEJ. Upon completion of NHEJ repair, DNA double strand-encircling Ku dimers have to be removed. The removal depends on ubiquitylation and proteasomal degradation of Ku80 by the ubiquitin E3 ligases RNF8. Here we report that RNF8 is a substrate of APC(Cdh1) and the latter keeps RNF8 level in check at DSBs to prevent premature turnover of Ku80.
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