Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination.
Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination.
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DOI：
10.3390/genes7090063
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发表时间：
2016-09-14
期刊：
影响因子：
3.5
通讯作者：
Mazin AV
中科院分区：
文献类型：
--
作者：
Hanamshet K;Mazina OM;Mazin AV
同源重组在维持基因组完整性方面起着重要作用。它负责修复最有害的DNA损伤，DNA双链断裂和链间DNA交联。HR功能对于减数分裂中同源染色体的正确分离、端粒的维持和解决停滞的复制叉也是必不可少的。HR的缺陷通常会导致遗传疾病和癌症。Rad 52是关键的HR蛋白之一，从酵母到人类在进化上是保守的。在酵母中，Rad 52对大多数HR事件很重要; Rad 52突变破坏DNA双链断裂的修复和靶向DNA整合。令人惊讶的是，在哺乳动物中，Rad 52敲除没有显示出显著的DNA修复或重组表型。然而，最近的工作表明，在人RAD 52的突变是合成致死的几个其他HR蛋白，包括BRCA 1和BRCA 2的突变。这些新发现表明Rad 52的重要后备作用，它补充了哺乳动物的主要HR机制。本文就Rad 52在HR中的活性和功能以及将人Rad 52作为BRCA 1和BRCA 2缺陷家族性乳腺癌和卵巢癌治疗靶点的可能性进行综述。
Homologous recombination (HR) plays an important role in maintaining genomic integrity. It is responsible for repair of the most harmful DNA lesions, DNA double-strand breaks and inter-strand DNA cross-links. HR function is also essential for proper segregation of homologous chromosomes in meiosis, maintenance of telomeres, and resolving stalled replication forks. Defects in HR often lead to genetic diseases and cancer. Rad52 is one of the key HR proteins, which is evolutionarily conserved from yeast to humans. In yeast, Rad52 is important for most HR events; Rad52 mutations disrupt repair of DNA double-strand breaks and targeted DNA integration. Surprisingly, in mammals, Rad52 knockouts showed no significant DNA repair or recombination phenotype. However, recent work demonstrated that mutations in human RAD52 are synthetically lethal with mutations in several other HR proteins including BRCA1 and BRCA2. These new findings indicate an important backup role for Rad52, which complements the main HR mechanism in mammals. In this review, we focus on the Rad52 activities and functions in HR and the possibility of using human RAD52 as therapeutic target in BRCA1 and BRCA2-deficient familial breast cancer and ovarian cancer.
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影响因子：
16.8
作者：
Bugreev, Dmitry V.;Hanaoka, Fumio;Mazin, Alexander V.
通讯作者：
Mazin, Alexander V.
DOI：
10.1073/pnas.82.17.5646
发表时间：
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影响因子：
11.1
作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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