Cockayne syndrome group B protein regulates DNA double-strand break repair and checkpoint activation

Nicole L. Batenburg, Elizabeth L Thompson, Eric A Hendrickson, Xu Dong Zhu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 ATPase activity impairs the recruitment of BRCA1, RPA and Rad51 proteins to damaged chromatin but promotes the formation of 53BP1-Rif1 damage foci in S and G2 cells. Depletion of 53BP1 rescues the formation of BRCA1 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 (DSBs) 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.

Original languageEnglish (US)
Pages (from-to)1399-1416
Number of pages18
JournalEMBO Journal
Volume34
Issue number10
DOIs
StatePublished - May 12 2015

Fingerprint

Cockayne Syndrome
Double-Stranded DNA Breaks
Chromatin
Repair
Chemical activation
DNA
Association reactions
Personnel Selection
Premature Aging
Mutation
Proteins
Automatic teller machines
Transcription
Mitosis
DNA Damage
Adenosine Triphosphatases
Aging of materials
Cells
Cell Line
Kinetics

Keywords

  • CSB
  • DNA damage checkpoint
  • DNA double-strand break repair

Cite this

Cockayne syndrome group B protein regulates DNA double-strand break repair and checkpoint activation. / Batenburg, Nicole L.; Thompson, Elizabeth L; Hendrickson, Eric A; Zhu, Xu Dong.

In: EMBO Journal, Vol. 34, No. 10, 12.05.2015, p. 1399-1416.

Research output: Contribution to journalArticle

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