Regulation of replication protein A functions in DNA mismatch repair by phosphorylation

Shuangli Guo, Yanbin Zhang, Fenghua Yuan, Yin Gao, Liya Gu, Isaac Wong, Guo Min Li

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Replication protein A (RPA) is involved in multiple stages of DNA mismatch repair (MMR); however, the modulation of its functions between different stages is unknown. We show here that phosphorylation likely modulates RPA functions during MMR. Unphosphorylated RPA initially binds to nicked heteroduplex DNA to facilitate assembly of the MMR initiation complex. The unphosphorylated protein preferentially stimulates mismatch-provoked excision, possibly by cooperatively binding to the resultant single-stranded DNA gap. The DNA-bound RPA begins to be phosphorylated after extensive excision, resulting in severalfold reduction in the DNA binding affinity of RPA. Thus, during the phase of repair DNA synthesis, the phosphorylated RPA readily disassociates from DNA, making the DNAtemplate available for DNA polymerase δ-catalyzed resynthesis. These observations support a model of how phosphorylation alters the DNA binding affinity of RPA to fulfill its differential requirement at the various stages of MMR.

Original languageEnglish (US)
Pages (from-to)21607-21616
Number of pages10
JournalJournal of Biological Chemistry
Volume281
Issue number31
DOIs
StatePublished - Aug 4 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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