Journal
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
Volume 90, Issue -, Pages 165-191Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-biochem-081420-095551
Keywords
break-induced replication; BIR; microhomology-mediated break-induced replication; MMBIR; alternative lengthening of telomeres; ALT; double-strand DNA breaks; DSBs; complex genome rearrangements; CRGs
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Funding
- National Institutes of Health [R35GM127006]
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DSB repair is essential for cell survival, but some pathways can be mutagenic and lead to genetic instability. BIR, a repair pathway for one-ended DSBs, has been studied in yeast and mammalian systems and is linked to high levels of genetic instability. Recent research has also revealed the role of microhomology-mediated BIR in complex genomic rearrangements underlying human pathologies.
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.
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