NYMC Faculty Publications

Role of PCNA and TLS Polymerases in D-loop Extension During Homologous Recombination in Humans

Author Type(s)

Faculty

DOI

10.1016/j.dnarep.2013.05.001

Journal Title

DNA Repair

First Page

691

Last Page

698

Document Type

Article

Publication Date

9-1-2013

Department

Biochemistry and Molecular Biology

Keywords

DNA Damage, DNA Polymerase III, DNA Replication, DNA, Single-Stranded, DNA-Directed DNA Polymerase, HeLa Cells, Homologous Recombination, Humans, Osmolar Concentration, Proliferating Cell Nuclear Antigen, RNA-Binding Protein FUS, Rad51 Recombinase, DNA Polymerase iota

Disciplines

Medicine and Health Sciences

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.

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