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Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans.

ABSTRACT: Homologous recombination (HR) is essential for maintaining genomic integrity, which is challenged by a wide variety of potentially lethal DNA lesions. Regardless of the damage type, recombination is known to proceed by RAD51-mediated D-loop formation, followed by DNA repair synthesis. Nevertheless, the participating polymerases and extension mechanism are not well characterized. Here, we present a reconstitution of this step using purified human proteins. In addition to Pol ?, TLS polymerases, including Pol ? and Pol ?, also can extend D-loops. In vivo characterization reveals that Pol ? and Pol ? are involved in redundant pathways for HR. In addition, the presence of PCNA on the D-loop regulates the length of the extension tracks by recruiting various polymerases and might present a regulatory point for the various recombination outcomes.

SUBMITTER: Sebesta M

PROVIDER: S-EPMC3744802 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans.

Sebesta Marek M Burkovics Peter P Juhasz Szilvia S Zhang Sufang S Szabo Judit E JE Lee Marietta Y W T MY Haracska Lajos L Krejci Lumir L

DNA repair 20130531 9

Homologous recombination (HR) is essential for maintaining genomic integrity, which is challenged by a wide variety of potentially lethal DNA lesions. Regardless of the damage type, recombination is known to proceed by RAD51-mediated D-loop formation, followed by DNA repair synthesis. Nevertheless, the participating polymerases and extension mechanism are not well characterized. Here, we present a reconstitution of this step using purified human proteins. In addition to Pol δ, TLS polymerases, i ...[more]

PMID: 23731732

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