期刊
GENES & DEVELOPMENT
卷 15, 期 8, 页码 945-954出版社
COLD SPRING HARBOR LAB PRESS
DOI: 10.1101/gad.882301
关键词
abasic sites; mutagenic bypass; yeast; DNA polymerase delta; DNA polymerase zeta
资金
- NIEHS NIH HHS [P30 ESO6676, P30 ES006676] Funding Source: Medline
- NIGMS NIH HHS [R01 GM032431, R01 GM058534, GM58534, GM19261] Funding Source: Medline
Abasic (AP) sites are one of the most frequently formed lesions in DNA, and they present a strong block to continued synthesis by the replicative DNA machinery. Here we show efficient bypass of an AP site by the combined action of yeast DNA polymerases delta and zeta. In this reaction, Pol delta inserts an A nucleotide opposite the AP site, and Pol zeta subsequently extends from the inserted nucleotide. Consistent with these observations, sequence analyses of mutations in the yeast CAN1(s) gene indicate that A is the nucleotide inserted most often opposite AP sites. The nucleotides C, G, and T are also incorporated, but much less frequently. Enzymes such as Rev1 and Pol eta may contribute to the insertion of these other nucleotides; the predominant role of Rev1 in AP bypass, however, is likely to be structural. Steady-state kinetic analyses show that Pol zeta is highly inefficient in incorporating nucleotides opposite the AP site, but it efficiently extends from nucleotides, particularly an A, inserted opposite this lesion. Thus, in eukaryotes, bypass of an AP site requires the sequential action of two DNA polymerases, wherein the extension step depends solely upon Pol zeta, but the insertion step can be quite varied, involving not only the predominant action of the replicative DNA polymerase, Pol delta, but also the less prominent role of various translesion synthesis polymerases.
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