TY - JOUR
T1 - Regulation of replication protein A functions in DNA mismatch repair by phosphorylation
AU - Guo, Shuangli
AU - Zhang, Yanbin
AU - Yuan, Fenghua
AU - Gao, Yin
AU - Gu, Liya
AU - Wong, Isaac
AU - Li, Guo Min
PY - 2006/8/4
Y1 - 2006/8/4
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M603504200
DO - 10.1074/jbc.M603504200
M3 - Article
C2 - 16731533
AN - SCOPUS:33746855461
SN - 0021-9258
VL - 281
SP - 21607
EP - 21616
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 31
ER -