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

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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 δ, TLS polymerases, including Pol η and Pol κ, also can extend D-loops. In vivo characterization reveals that Pol η and Pol κ 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. © 2013 The Authors.

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Sebesta, M., Burkovics, P., Juhasz, S., Zhang, S., Szabo, J. E., Lee, M. Y. W. T., … Krejci, L. (2013). Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans. DNA Repair, 12(9), 691–698. https://doi.org/10.1016/j.dnarep.2013.05.001

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