Authors:	Kellner, Vanessa Luke, Brian
Title:	Molecular and physiological consequences of faulty eukaryotic ribonucleotide excision repair
Online publication date:	20-May-2022
Year of first publication:	2020
Language:	english
Abstract:	The duplication of the eukaryotic genome is an intricate process that has to be tightly safe-guarded. One of the most frequently occurring errors during DNA synthesis is the mis-insertion of a ribonucleotide instead of a deoxyribonucleotide. Ribonucleotide excision repair (RER) is initiated by RNase H2 and results in error-free removal of such mis-incorporated ribonucleotides. If left unrepaired, DNA-embedded ribonucleotides result in a variety of alterations within chromosomal DNA, which ultimately lead to genome instability. Here, we review how genomic ribonucleotides lead to chromosomal aberrations and discuss how the tight regulation of RER timing may be important for preventing unwanted DNA damage. We describe the structural impact of unrepaired ribonucleotides on DNA and chromatin and comment on the potential consequences for cellular fitness. In the context of the molecular mechanisms associated with faulty RER, we have placed an emphasis on how and why increased levels of genomic ribonucleotides are associated with severe autoimmune syndromes, neuropathology, and cancer. In addition, we discuss therapeutic directions that could be followed for pathologies associated with defective removal of ribonucleotides from double-stranded DNA.
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-7010
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	The EMBO journal 39
Pages or article number:	e102309
Publisher:	EMBO Press
Publisher place:	Heidelberg
Issue date:	2020
ISSN:	1460-2075
Publisher DOI:	10.15252/embj.2019102309
Appears in collections:	JGU-Publikationen