The single-strand DNA binding activity of human PC4 preventsmutagenesis and killing by oxidative DNA damage
Human positive cofactor 4 (PC4) is a transcriptional coactivator with a highly conserved single-strand DNA (ssDNA) binding domain of unknown function. We identified PC4 as a suppressor of the oxidative mutator phenotype of the Escherichia coli fpg mutY mutant and demonstrate that this suppression requires its ssDNA binding activity. Yeast mutants lacking their PC4 ortholog Sub1 are sensitive to hydrogen peroxide and exhibit spontaneous and peroxide induced hypermutability. PC4 expression suppresses the peroxide sensitivity of the yeast sub l{Delta} mutant, suggesting that the human protein has a similar function. A role for yeast and human proteins in DNA repair is suggested by the demonstration that Sub1 acts in a peroxide-resistance pathway involving Rad2 and by the physical interaction of PC4 with the human Rad2 homolog XPG. We show XPG recruits PC4 to a bubble-containing DNA substrate with resulting displacement of XPG and formation of a PC4-DNA complex. We discuss the possible requirement for PC4 in either global or transcription-coupled repair of oxidative DNA damage to mediate the release of XPG bound to its substrate.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Director, Office of Science. Office of Biological andEnvironmental Research. Life Sciences Division; National Institutes ofHealth
- DOE Contract Number:
- DE-AC02-05CH11231; NIHGM56420, CA63503
- OSTI ID:
- 886816
- Report Number(s):
- LBNL-54618; MCEBD4; R&D Project: 0; BnR: YN1901000; TRN: US200616%%1191
- Journal Information:
- Molecular and Cellular Biology, Vol. 24, Issue 13; Related Information: Journal Publication Date: July 2004; ISSN 0270-7306
- Country of Publication:
- United States
- Language:
- English
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