TY - JOUR
T1 - Repair of DNA Breaks by Break-Induced Replication
AU - Kockler, Z. W.
AU - Osia, B.
AU - Lee, R.
AU - Musmaker, K.
AU - Malkova, A.
N1 - Publisher Copyright:
Copyright © 2021 by Annual Reviews. All rights reserved.
PY - 2021/6/20
Y1 - 2021/6/20
N2 - 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.
AB - 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.
KW - ALT
KW - Alternative lengthening of telomeres
KW - BIR
KW - Break-induced replication
KW - CRGs
KW - Complex genome rearrangements
KW - DSBs
KW - Double-strand DNA breaks
KW - MMBIR
KW - Microhomology-mediated break-induced replication
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U2 - 10.1146/annurev-biochem-081420-095551
DO - 10.1146/annurev-biochem-081420-095551
M3 - Review article
C2 - 33792375
AN - SCOPUS:85108565791
SN - 0066-4154
VL - 90
SP - 165
EP - 191
JO - Annual Review of Biochemistry
JF - Annual Review of Biochemistry
ER -