Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon

Epshtein, Anastasiya; Potenski, Catherine J.; Klein, Hannah L.

Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon

Authors:

Anastasiya Epshtein¹, Catherine J. Potenski², and Hannah L. Klein¹

doi: 10.15698/mic2016.06.506
Volume 3, pp. 248 to 254, published 15/05/2016.

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Affiliations:

¹ Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.

² Nature Publishing Group, One New York Plaza, New York, New York 10004, USA.

Keywords:

RNase H2, recombination, rNMP, DNA polymerase.

Corresponding Author(s):

Hannah L. Klein, Department of Biochemistry and Molecular Pharmacology, Smilow 201C, 522 First Avenue, NYU Langone Medical Center; New York, NY 10016, USA hannah.klein@nyumc.org

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Anastasiya Epshtein, Catherine J. Potenski, and Hannah L. Klein (2016). Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon. Microbial Cell 3(6): 248-254. doi: 10.15698/mic2016.06.506

© 2016 Epshtein et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Ribonucleotides can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. RNA:DNA hybrids are removed by RNase H enzymes. Single rNMPs in DNA are removed by RNase H2 and if they remain on the leading strand, can lead to mutagenesis in a Top1-dependent pathway. rNMPs in DNA can also stimulate genome instability, among which are homologous recombination gene conversion events. We previously found that, similar to the rNMP-stimulated mutagenesis, rNMP-stimulated recombination was also Top1-dependent. However, in contrast to mutagenesis, we report here that recombination is not stimulated by rNMPs incorporated by the replicative polymerase epsilon. Instead, recombination seems to be stimulated by multiple contiguous rNMPs, which may arise from R-loops or replication priming events.