Research Project
Grant-in-Aid for Scientific Research (C)
In eulcaryotic cells, DNA polymerase a(pol a)initiates DNA synthesis at replication origins and at the 5'-ends of Okazaki fragments. Pol a lacks proofreading activity for correcting nucleotide misincorporation errors, but it extends mismatched 31-termini inefficiently. This can lead to premature termination of mismatched/misaligned DNA primers. The mutator polymerase L868F pol a catalyzes nucleotide misincorporation and misextension more frequently than wild type pol a. We have shown misaligned primers, but not the mismatched primers, generated by pol a can be extended by pol C in a reaction that requires PCNA. A yeast strain carrying L868F or L868M allele of pol a generated +1 frameshifts at a high rate, and this rate was decreased in strains lacking the catalytic subunit of pol C. Mutations were dependent on PCNA Lys164, and were downstream of the RAD18. Furthermore, inactivation of pol S exonuclease increased the proportion of pol t -dependent +1 frameshifts. These data suggest that PCNA and pol t cooperate in a replication error promoting pathway that may be targeted to misalignment errors. In this context, pol a PCNA-, and pol C -dependent DNA synthesis may be a source of genetic variation which drives evolution or a source of mutations with potential to cause dysfunction and disease
All 2008 2007 2006
All Journal Article (30 results) (of which Peer Reviewed: 14 results) Presentation (17 results)
Biosci. Biotech. Biochem. (In press)
Biosci. Biotech. Biochem (in press)
10027525010
Oncogene 26
Pages: 1802-1810
FEBS Lett 581
Pages: 1800-1801
Pages: 6099-6105
J Neurochem 102
Pages: 1585-1594
Cancer Res. 67
Pages: 11158-11165
Cancer Res 67
Pages: 11158-65
oncogene (In press)
FEBS Letters (In press)
Curr. Biol. 16
Pages: 202-207
Leukemia 20
Pages: 2042-2046
Curr Biol 16
Current Biology 16
American Journal of Human Genetics 78・1
Pages: 125-129
Neurology 67・4
Pages: 607-613
Neurology 66・10
Pages: 1602-1604
