Authors:	Schindler, Natalie Tonn, Matthias Kellner, Vanessa Fung, Jia Jun Lockhart, Arianna Vydzhak, Olga Juretschke, Thomas Möckel, Stefanie Beli, Petra Khmelinskii, Anton Luke, Brian
Title:	Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase
Online publication date:	15-Jun-2023
Year of first publication:	2023
Language:	english
Abstract:	Single ribonucleoside monophosphates (rNMPs) are transiently present in eukaryotic genomes. The RNase H2-dependent ribonucleotide excision repair (RER) pathway ensures error-free rNMP removal. In some pathological conditions, rNMP removal is impaired. If these rNMPs hydrolyze during, or prior to, S phase, toxic single-ended double-strand breaks (seDSBs) can occur upon an encounter with replication forks. How such rNMP-derived seDSB lesions are repaired is unclear. We expressed a cell cycle phase restricted allele of RNase H2 to nick at rNMPs in S phase and study their repair. Although Top1 is dispensable, the RAD52 epistasis group and Rtt101Mms1-Mms22 dependent ubiquitylation of histone H3 become essential for rNMP-derived lesion tolerance. Consistently, loss of Rtt101Mms1-Mms22 combined with RNase H2 dysfunction leads to compromised cellular fitness. We refer to this repair pathway as nick lesion repair (NLR). The NLR genetic network may have important implications in the context of human pathologies.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9181
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Nature Communications 14
Pages or article number:	1227
Publisher:	Springer Nature
Publisher place:	London
Issue date:	2023
ISSN:	2041-1723
Publisher DOI:	10.1038/s41467-023-36866-6
Appears in collections:	DFG-491381577-G