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Cockayne syndrome group B protein regulates DNA double‐strand break repair and checkpoint activation
Author(s) -
Batenburg Nicole L,
Thompson Elizabeth L,
Hendrickson Eric A,
Zhu XuDong
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490041
Subject(s) - biology , cockayne syndrome , chromatin , dna damage , dna repair , rad51 , microbiology and biotechnology , premature aging , mitosis , mutation , nucleotide excision repair , dna , genetics , gene
Mutations of CSB account for the majority of Cockayne syndrome ( CS ), a devastating hereditary disorder characterized by physical impairment, neurological degeneration and segmental premature aging. Here we report the generation of a human CSB ‐knockout cell line. We find that CSB facilitates HR and represses NHEJ . Loss of CSB or a CS ‐associated CSB mutation abrogating its ATP ase activity impairs the recruitment of BRCA 1, RPA and Rad51 proteins to damaged chromatin but promotes the formation of 53 BP 1‐Rif1 damage foci in S and G2 cells. Depletion of 53 BP 1 rescues the formation of BRCA 1 damage foci in CSB ‐knockout cells. In addition, knockout of CSB impairs the ATM ‐ and Chk2‐mediated DNA damage responses, promoting a premature entry into mitosis. Furthermore, we show that CSB accumulates at sites of DNA double‐strand breaks ( DSB s) in a transcription‐dependent manner. The kinetics of DSB ‐induced chromatin association of CSB is distinct from that of its UV ‐induced chromatin association. These results reveal novel, important functions of CSB in regulating the DNA DSB repair pathway choice as well as G2/M checkpoint activation.