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RB stabilizes XPC and promotes cellular NER.

Authors
  • Hardy, Tabitha M
  • Kumar, Ma Suresh
  • Smith, Martin L
Type
Published Article
Journal
Anticancer Research
Publisher
International Institute of Anticancer Research
Publication Date
Jul 01, 2010
Volume
30
Issue
7
Pages
2483–2488
Identifiers
PMID: 20682972
Source
Medline
License
Unknown

Abstract

It has long been thought that the G(1)/S cell cycle checkpoint allows time for DNA repair by delaying S-phase entry. The p53 tumor suppressor pathway regulates the G(1)/S checkpoint by regulating the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), but p53 also regulates the nucleotide excision DNA repair protein XPC. Here, using p53-null cell lines we show that additional mechanisms stabilize XPC protein and promote nucleotide excision repair (NER) in concert with the G(1)/S checkpoint. At least one mechanism to stabilize and destabilize XPC involves ubiquitin-mediated degradation of XPC, as the ubiquitin ligase inhibitor MG-132 blocked XPC degradation. The retinoblastoma protein RB, in its unphosphorylated form actually stabilized XPC and promoted NER as measured by host cell reactivation experiments. The data suggest that XPC protein and XPC-mediated NER are tightly linked to the G(1)/S checkpoint, even in cells lacking functional p53.

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