Premium
Opposing effects of the UV lesion repair protein XPA and UV bypass polymerase η on ATR checkpoint signaling
Author(s) -
Bomgarden Ryan D,
Lupardus Patrick J,
Soni Deena V,
Yee MuhChing,
Ford James M,
Cimprich Karlene A
Publication year - 2006
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 - 10.1038/sj.emboj.7601123
Subject(s) - library science , biology , computer science
An essential component of the ATR (ataxia telangiectasia‐mutated and Rad3‐related)‐activating structure is single‐stranded DNA. It has been suggested that nucleotide excision repair (NER) can lead to activation of ATR by generating such a signal, and in yeast, DNA damage processing through the NER pathway is necessary for checkpoint activation during G1. We show here that ultraviolet (UV) radiation‐induced ATR signaling is compromised in XPA‐deficient human cells during S phase, as shown by defects in ATRIP (ATR‐interacting protein) translocation to sites of UV damage, UV‐induced phosphorylation of Chk1 and UV‐induced replication protein A phosphorylation and chromatin binding. However, ATR signaling was not compromised in XPC‐, CSB‐, XPF‐ and XPG‐deficient cells. These results indicate that damage processing is not necessary for ATR‐mediated S‐phase checkpoint activation and that the lesion recognition function of XPA may be sufficient. In contrast, XP‐V cells deficient in the UV bypass polymerase η exhibited enhanced ATR signaling. Taken together, these results suggest that lesion bypass and not lesion repair may raise the level of UV damage that can be tolerated before checkpoint activation, and that XPA plays a critical role in this activation.