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Repair of DNA Breaks by Break-Induced Replication
Journal article   Open access   Peer reviewed

Repair of DNA Breaks by Break-Induced Replication

Z W Kockler, B Osia, R Lee, K Musmaker and A Malkova
Annual review of biochemistry, Vol.90(1), pp.165-191
06/20/2021
DOI: 10.1146/annurev-biochem-081420-095551
PMCID: PMC9629446
PMID: 33792375
url
https://doi.org/10.1146/annurev-biochem-081420-095551View
Published (Version of record) Open Access

Abstract

Double-strand DNA breaks (DSBs) are the most lethal type of DNA damage, making DSB repair critical for cell survival. However, some DSB repair pathways are mutagenic and promote genome rearrangements, leading to genome destabilization. One such pathway is break-induced replication (BIR), which repairs primarily one-ended DSBs, similar to those formed by collapsed replication forks or telomere erosion. BIR is initiated by the invasion of a broken DNA end into a homologous template, synthesizes new DNA within the context of a migrating bubble, and is associated with conservative inheritance of new genetic material. This mode of synthesis is responsible for a high level of genetic instability associated with BIR. Eukaryotic BIR was initially investigated in yeast, but now it is also actively studied in mammalian systems. Additionally, a significant breakthrough has been made regarding the role of microhomology-mediated BIR in the formation of complex genomic rearrangements that underly various human pathologies.
DNA Repair DNA Replication Mutation Animals DNA Breaks, Double-Stranded DNA End-Joining Repair Humans Mammals - genetics Telomere Homeostasis - genetics Yeasts - genetics

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