Comprehensive analysis of cis- and trans-acting factors affecting ectopic Break-Induced Replication

Break-induced replication (BIR) is a highly mutagenic eukaryotic homologous DNA recombination pathway that repairs one-ended DNA double strand breaks such as broken DNA replication forks and eroded telomeres. While searching for cis-acting factors regulating ectopic BIR efficiency, we found that ect...

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Published inPLoS genetics Vol. 18; no. 6; p. e1010124
Main Authors Uribe-Calvillo, Tannia, Maestroni, Laetitia, Marsolier, Marie-Claude, Khadaroo, Basheer, Arbiol, Christine, Schott, Jonathan, Llorente, Bertrand
Format Journal Article
LanguageEnglish
Published San Francisco Public Library of Science 01.06.2022
Public Library of Science (PLoS)
Subjects
Biology and Life Sciences
Chromosomes
Deoxyribonucleic acid
Diploids
DNA
DNA biosynthesis
DNA damage
DNA helicase
DNA polymerase
DNA repair
Efficiency
Genomes
Homologous recombination
Life Sciences
Mutation
Replication forks
Research and analysis methods
RNA polymerase
Telomerase
Telomeres
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Summary:Break-induced replication (BIR) is a highly mutagenic eukaryotic homologous DNA recombination pathway that repairs one-ended DNA double strand breaks such as broken DNA replication forks and eroded telomeres. While searching for cis-acting factors regulating ectopic BIR efficiency, we found that ectopic BIR efficiency is the highest close to chromosome ends. The variations of ectopic BIR efficiency as a function of the length of DNA to replicate can be described as a combination of two decreasing exponential functions, a property in line with repeated cycles of strand invasion, elongation and dissociation that characterize BIR. Interestingly, the apparent processivity of ectopic BIR depends on the length of DNA already synthesized. Ectopic BIR is more susceptible to disruption during the synthesis of the first ~35–40 kb of DNA than later, notably when the template chromatid is being transcribed or heterochromatic. Finally, we show that the Srs2 helicase promotes ectopic BIR from both telomere proximal and telomere distal regions in diploid cells but only from telomere proximal sites in haploid cells. Altogether, we bring new light on the factors impacting a last resort DNA repair pathway.
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PMCID: PMC9249352
Current address: Toulouse Biotechnology Institute, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France
The authors have declared that no competing interests exist.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1010124