Human RECQL5: guarding the crossroads of DNA replication and transcription and providing backup capability.
Human RECQL5: guarding the crossroads of DNA replication and transcription and providing backup capability.
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DOI：
10.3109/10409238.2013.792770
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发表时间：
2013-05
影响因子：
6.5
通讯作者：
Bohr VA
中科院分区：
文献类型：
--
作者：
Popuri V;Tadokoro T;Croteau DL;Bohr VA
DNA解旋酶是一种普遍存在的酶，它催化双链DNA解链，参与所有需要接触单链DNA的代谢过程，包括DNA复制、修复、重组和RNA转录。RecQ解旋酶是一个保守的DNA解旋酶家族，在维持基因组稳定性方面发挥着高度专门化和重要的作用。人类五个RecQ解旋酶中的三个BLM、WRN和RECQL4的突变与Bloom综合征、Werner综合征和Rothmund-Thomson综合征相关，这些遗传病的特征是染色体不稳定、过早衰老和易患癌症。人类RECQL5的生物学作用仅被部分了解，RECQL5尚未与任何人类疾病相关。非法重组和复制压力是人类癌症的特征，也是基因组不稳定和细胞死亡的常见煽动者。Recq15基因敲除小鼠更容易罹患癌症，并表现出更高的染色体不稳定性。Recq15基因缺陷的小鼠胚胎成纤维细胞对喜树碱敏感，并显示姐妹染色单体交换水平升高。与其他人类RecQ解旋酶不同，RECQL5被招募到单链DNA断裂，并被认为在RNA转录中发挥重要作用。在这里，我们综述了RECQL5在DNA复制、重组和转录的十字路口所起的作用，并提出在缺乏其他DNA解旋酶的情况下，人类RECQL5提供了重要的备份功能。
DNA helicases are ubiquitous enzymes that catalyze unwinding of duplex DNA and function in all metabolic processes in which access to single-stranded DNA is required, including DNA replication, repair, recombination and RNA transcription. RecQ helicases are a conserved family of DNA helicases that display highly specialized and vital roles in the maintenance of genome stability. Mutations in three of the five human RecQ helicases, BLM, WRN and RECQL4 are associated with the genetic disorders Bloom syndrome, Werner syndrome and Rothmund-Thomson syndrome that are characterized by chromosomal instability, premature aging and predisposition to cancer. The biological role of human RECQL5 is only partially understood and RECQL5 has not yet been associated with any human disease. Illegitimate recombination and replication stress are hallmarks of human cancers and common instigators for genomic instability and cell death. Recql5 knockout mice are cancer prone and show increased chromosomal instability. Recql5-deficient mouse embryonic fibroblasts are sensitive to camptothecin and display elevated levels of sister chromatid exchanges. Unlike other human RecQ helicases, RECQL5 is recruited to single-stranded DNA breaks and is also proposed to play an essential role in RNA transcription. Here, we review the established roles of RECQL5 at the cross roads of DNA replication, recombination and transcription, and propose that human RECQL5 provides important backup functions in the absence of other DNA helicases.