Break induced replication in eukaryotes: mechanisms, functions, and consequences.
Break induced replication in eukaryotes: mechanisms, functions, and consequences.
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DOI：
10.1080/10409238.2017.1314444
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发表时间：
2017-08
影响因子：
6.5
通讯作者：
Malkova A
中科院分区：
文献类型：
--
作者：
Sakofsky CJ;Malkova A
断裂诱导复制（BIR）是一条重要的DNA单端双链断裂修复途径。这种类型的DSB断裂通常发生在折叠的复制叉或被侵蚀的端粒处。BIR通过断裂的DNA末端侵入同源模板，随后启动DNA合成来启动，这可以进行数百种酶。这种合成与S期复制截然不同，因为BIR不是复制叉，而是通过迁移气泡进行，并且与新合成DNA的保守遗传有关。这种不寻常的DNA复制模式是与BIR相关的频繁遗传不稳定性的原因，包括超诱变，其可导致突变簇的形成、杂合性的广泛丢失、染色体易位、拷贝数变异和复杂的基因组重排。除了最初用于研究真核生物BIR的芽殖酵母实验系统之外，最近在包括人类在内的不同生物体中的研究已经提供了在不同细胞环境中引发的BIR的多个实例，包括在端粒酶不存在的情况下折叠的复制叉和端粒维持。此外，在理解微同源介导的BIR（MMBIR）方面已经取得了重大进展，该微同源介导的BIR可以促进复杂的染色体重排，包括与癌症相关的染色体重排和导致人类许多神经系统疾病的染色体重排。
Break-Induced Replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases. This synthesis is drastically different from S-phase replication in that instead of a replication fork, BIR proceeds via a migrating bubble and is associated with conservative inheritance of newly synthesized DNA. This unusual mode of DNA replication is responsible for frequent genetic instabilities associated with BIR, including hyper-mutagenesis, which can lead to the formation of mutation clusters, extensive loss of heterozygosity, chromosomal translocations, copy-number variations, and complex genomic rearrangements. In addition to budding yeast experimental systems that were initially employed to investigate eukaryotic BIR, recent studies in different organisms including humans, have provided multiple examples of BIR initiated within different cellular contexts, including collapsed replication fork and telomere maintenance in the absence of telomerase. In addition, significant progress has been made towards understanding microhomology-mediated BIR (MMBIR) that can promote complex chromosomal rearrangements, including those associated with cancer and those leading to a number of neurological disorders in humans.
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影响因子：
4.5
作者：
Chung WH;Zhu Z;Papusha A;Malkova A;Ira G
通讯作者：
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影响因子：
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作者：
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64.5
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通讯作者：
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11.4
作者：
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通讯作者：
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