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The anaphase promoting complex promotes NHEJ repair through stabilizing Ku80 at DNA damage sites.


ABSTRACT: 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 APCCdh1 and the latter keeps RNF8 level in check at DSBs to prevent premature turnover of Ku80.

SUBMITTER: Ma C 

PROVIDER: S-EPMC6110584 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The anaphase promoting complex promotes NHEJ repair through stabilizing Ku80 at DNA damage sites.

Ma Chengxian C   Ha Kyungsoo K   Kim Min-Su MS   Noh Young-Woock YW   Lin Han H   Tang Lichun L   Zhu Qing Q   Zhang Dan D   Chen Huan H   Han Suxia S   Zhang Pumin P  

Cell cycle (Georgetown, Tex.) 20180718 9


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  ...[more]

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