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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]

PMID: 29895199

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The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites.

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DNA-PKcs-dependent phosphorylation of RECQL4 promotes NHEJ by stabilizing the NHEJ machinery at DNA double-strand breaks.

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Histone H2B ubiquitination promotes the function of the anaphase-promoting complex/cyclosome in Schizosaccharomyces pombe.

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Anaphase-promoting complex-dependent control of cell identity

Project description:Tissue development and homeostasis rely on the proliferation of progenitor cells, whose identities are established by tightly controlled gene expression networks. However, mRNA synthesis is inhibited during mitosis, and the transcriptional programs that define a cell type must be restarted upon entry into each new cell cycle; how this is accomplished is poorly understood. Here, we identified a ubiquitin-dependent mechanism that integrates gene expression with cell division to preserve cell identity. We found that WDR5 and TBP, which bind active promoters during interphase, recruit the E3 ligase anaphase-promoting complex (APC/C) to specific transcription start sites during mitosis. This allows the APC/C to locally decorate histones with K11/K48-linked ubiquitin chains, which destabilizes nucleosomes and ensures continued gene expression in the next cell cycle. Mitotic exit and transcription re-initiation are therefore controlled by the same essential regulator, the APC/C, which provides a robust mechanism to maintain cell identity through cell division.

2020-02-03 | GSE122298 | GEO

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