PCNA Is Required for Initiation of Recombination-Associated DNA Synthesis by DNA Polymerase δ

Genetic recombination ensures proper chromosome segregation during meiosis and is essential for genome stability and tumor suppression. DNA synthesis after Rad51-mediated DNA strand invasion is a crucial step during recombination. PCNA is known as the processivity clamp for DNA polymerases. Here, we...

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Published in:Molecular cell Vol. 36; no. 4; pp. 704 - 713
Main Authors: Li, Xuan, Stith, Carrie M., Burgers, Peter M., Heyer, Wolf-Dietrich
Format: Journal Article
Language:English
Published: United States Elsevier Inc 25-11-2009
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Summary:Genetic recombination ensures proper chromosome segregation during meiosis and is essential for genome stability and tumor suppression. DNA synthesis after Rad51-mediated DNA strand invasion is a crucial step during recombination. PCNA is known as the processivity clamp for DNA polymerases. Here, we report the surprising observation that PCNA is specifically required to initiate recombination-associated DNA synthesis in the extension of the 3′ end of the invading strand in a D loop. We show using a reconstituted system of yeast Rad51, Rad54, RPA, PCNA, RFC, and DNA polymerase δ that loading of PCNA by RFC targets DNA polymerase δ to the D loop formed by Rad51 protein, allowing efficient utilization of the invading 3′ end and processive DNA synthesis. We conclude that PCNA has a specific role in the initiation of recombination-associated DNA synthesis and that DNA polymerase δ promotes recombination-associated DNA synthesis.
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Present address: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2009.09.036