Document Detail


Direct involvement of the tumor suppressor p53 in nucleotide excision repair.
MedLine Citation:
PMID:  18343205     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The tumor suppressor p53 enhances repair of UVC-induced DNA damage. The comet-NE assay, a conventional alkaline comet assay which includes a nuclear digestion step, was used to examine the effects of p53 on the excision activity of nuclear extracts (NEs). In contrast with untreated NEs, NEs immunodepleted of p53 or NEs of p53-null cells were unable to excise UVC-induced DNA adducts. Introduction of p53 by transfection restored the excision activity to NEs of p53-null cells. Deletion of the N-terminal 99 amino acids and/or the C-terminal 85 amino acids of p53 barely affected the excision activity, whereas further deletion of the C-terminus of p53 by another 10 amino acids completely abolished the excision activity of NEs. Immunostaining following localized UV irradiation was used to examine the effects of p53 on the recruitment of repair proteins for nucleotide excision repair (NER). Although recruitment of XPC occurred regardless of the presence of p53, the recruitment of XPB was p53-dependent. However, p53 with the 95 amino acid deletion at its C-terminus was unable to support this recruitment of XPB. Consistently, intact p53 (but not the C-terminal 95 residue truncated version) was detected in co-immunoprecipitation assays with an anti-XPB antibody. These results support the hypothesis that p53 facilitates NER through direct involvement by protein-protein interactions.
Authors:
Yu-Ching Chang; Kun-Yan Jan; Chun-An Cheng; Chu-Bin Liao; Yin-Chang Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-14
Journal Detail:
Title:  DNA repair     Volume:  7     ISSN:  1568-7864     ISO Abbreviation:  DNA Repair (Amst.)     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-28     Completed Date:  2008-07-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101139138     Medline TA:  DNA Repair (Amst)     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  751-61     Citation Subset:  IM    
Affiliation:
Institute of Molecular Medicine, National Tsing-Hua University, Hsin-Chu 30043, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / metabolism
Cell Line, Tumor
DNA Helicases / metabolism
DNA Repair*
DNA-Binding Proteins / metabolism
Genes, p53 / genetics
Humans
Pyrimidine Dimers / metabolism
Sequence Deletion
Tumor Suppressor Protein p53 / metabolism*
Chemical
Reg. No./Substance:
0/Amino Acids; 0/DNA-Binding Proteins; 0/Pyrimidine Dimers; 0/Tumor Suppressor Protein p53; 146045-44-5/XPBC-ERCC-3 protein; EC 3.6.1.-/DNA Helicases

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