Department of Biology, University of Iowa, Iowa City, Iowa 52242, USA; email:
Annu Rev Biochem. 2021 Jun 20;90:165-191. doi: 10.1146/annurev-biochem-081420-095551. Epub 2021 Apr 1.
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.
双链 DNA 断裂 (DSB) 是最致命的 DNA 损伤类型，因此 DSB 修复对于细胞存活至关重要。然而，一些 DSB 修复途径具有诱变作用，并促进基因组重排，导致基因组不稳定性。其中一种途径是断裂诱导复制 (BIR)，它主要修复单端 DSB，类似于由复制叉崩溃或端粒侵蚀形成的 DSB。BIR 是由断裂的 DNA 末端侵入同源模板引发的，在迁移泡的背景下合成新的 DNA，并与新遗传物质的保守遗传有关。这种合成模式是导致与 BIR 相关的高水平遗传不稳定性的原因。真核生物的 BIR 最初在酵母中进行了研究，但现在在哺乳动物系统中也在积极研究。此外，在微同源介导的 BIR 在形成各种人类病理基础的复杂基因组重排中的作用方面取得了重大突破。
