DNA structure-specific priming of ATR activation by DNA-PKcs.

Details

Ressource 1Download: BIB_801B21C4627F.P001.pdf (1878.48 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_801B21C4627F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
DNA structure-specific priming of ATR activation by DNA-PKcs.
Journal
Journal of Cell Biology
Author(s)
Vidal-Eychenié S., Décaillet C., Basbous J., Constantinou A.
ISSN
1540-8140 (Electronic)
ISSN-L
0021-9525
Publication state
Published
Issued date
2013
Volume
202
Number
3
Pages
421-429
Language
english
Abstract
Three phosphatidylinositol-3-kinase-related protein kinases implement cellular responses to DNA damage. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia-telangiectasia mutated respond primarily to DNA double-strand breaks (DSBs). Ataxia-telangiectasia and RAD3-related (ATR) signals the accumulation of replication protein A (RPA)-covered single-stranded DNA (ssDNA), which is caused by replication obstacles. Stalled replication intermediates can further degenerate and yield replication-associated DSBs. In this paper, we show that the juxtaposition of a double-stranded DNA end and a short ssDNA gap triggered robust activation of endogenous ATR and Chk1 in human cell-free extracts. This DNA damage signal depended on DNA-PKcs and ATR, which congregated onto gapped linear duplex DNA. DNA-PKcs primed ATR/Chk1 activation through DNA structure-specific phosphorylation of RPA32 and TopBP1. The synergistic activation of DNA-PKcs and ATR suggests that the two kinases combine to mount a prompt and specific response to replication-born DSBs.
Pubmed
Web of science
Open Access
Yes
Create date
02/09/2013 8:36
Last modification date
20/08/2019 14:40
Usage data