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

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Authors

ŠEBESTA Marek BURKOVICS Peter JUHASZ Szilvia ZHANG Sufang SZABO Judit LEE Marietta Y. W. T. HARACSKA Lajos KREJČÍ Lumír

Year of publication 2013
Type Article in Periodical
Magazine / Source DNA Repair
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1016/j.dnarep.2013.05.001
Field Genetics and molecular biology
Keywords TLS polymerases; Homologous recombination; DNA repair synthesis; D-loop; Reconstitution
Description 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 delta, TLS polymerases, including Pol eta and Pol kappa, also can extend D-loops. In vivo characterization reveals that Pol eta and Pol kappa 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.
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