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Autoren: Kellner, Vanessa
Luke, Brian
Titel: Molecular and physiological consequences of faulty eukaryotic ribonucleotide excision repair
Online-Publikationsdatum: 20-Mai-2022
Sprache des Dokuments: Englisch
Zusammenfassung/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-Sachgruppe: 570 Biowissenschaften
570 Life sciences
Veröffentlichende Institution: Johannes Gutenberg-Universität Mainz
Organisationseinheit: FB 10 Biologie
Veröffentlichungsort: Mainz
Version: Published version
Publikationstyp: Zeitschriftenaufsatz
Nutzungsrechte: CC BY
Informationen zu den Nutzungsrechten:
Zeitschrift: The EMBO journal
Seitenzahl oder Artikelnummer: e102309
Verlag: EMBO Press
Verlagsort: Heidelberg
Erscheinungsdatum: 2020
ISSN: 1460-2075
DOI der Originalveröffentlichung: 10.15252/embj.2019102309
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