Translesion synthesis polymerases are dispensable for C. elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining.
Publication Date
2020-04Journal Title
PLoS Genet
ISSN
1553-7390
Publisher
Public Library of Science (PLoS)
Volume
16
Issue
4
Language
en
Type
Article
This Version
VoR
Metadata
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van Bostelen, I., van Schendel, R., Romeijn, R., & Tijsterman, M. (2020). Translesion synthesis polymerases are dispensable for C. elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining.. PLoS Genet, 16 (4) https://doi.org/10.1371/journal.pgen.1008759
Abstract
Bases within DNA are frequently damaged, producing obstacles to efficient and accurate DNA replication by replicative polymerases. Translesion synthesis (TLS) polymerases, via their ability to catalyze nucleotide additions to growing DNA chains across DNA lesions, promote replication of damaged DNA, thus preventing checkpoint activation, genome instability and cell death. In this study, we used C. elegans to determine the contribution of TLS activity on long-term stability of an animal genome. We monitored and compared the types of mutations that accumulate in REV1, REV3, POLH1 and POLK deficient animals that were grown under unchallenged conditions. We also addressed redundancies in TLS activity by combining all deficiencies. Remarkably, animals that are deficient for all Y-family polymerases as well as animals that have lost all TLS activity are viable and produce progeny, demonstrating that TLS is not essential for animal life. Whole genome sequencing analyses, however, reveal that TLS is needed to prevent genomic scars from accumulating. These scars, which are the product of polymerase theta-mediated end joining (TMEJ), are found overrepresented at guanine bases, consistent with TLS suppressing DNA double-strand breaks (DSBs) from occurring at replication-blocking guanine adducts. We found that in C. elegans, TLS across spontaneous damage is predominantly error free and anti-clastogenic, and thus ensures preservation of genetic information.
Keywords
Research Article, Research and analysis methods, Biology and life sciences
Identifiers
pgenetics-d-20-00260
External DOI: https://doi.org/10.1371/journal.pgen.1008759
This record's URL: https://www.repository.cam.ac.uk/handle/1810/305100
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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