Probing Genome Maintenance Functions of human RECQ1.
Probing Genome Maintenance Functions of human RECQ1.
复制标题
探索人类 RECQ1 的基因组维护功能。
DOI：
10.5936/csbj.201303014
复制
发表时间：
2013
影响因子：
6
通讯作者：
Sharma S
中科院分区：
文献类型：
--
作者：
Sami F;Sharma S
RecQ解旋酶是一个高度保守的DNA解旋酶家族，在所有生命王国中保护基因组稳定性方面发挥关键作用。人类RecQ同源物包括RECQ 1、BLM、WRN、RECQ 4和RECQ 5 β。尽管个体RecQ相关疾病的特征在于包括生长缺陷（Bloom综合征和Rothmund Thomson综合征）到过早衰老（Werner综合征）的各种临床特征，但所有这些患者都具有癌症易感性的高风险。在这里，我们提出了一个概述RECQ 1解旋酶，最丰富的，但在人类中的特点差RecQ同系物阐明功能的最新进展。与基因组稳定性维持中的保守作用一致，RECQ 1的缺乏导致自发姐妹染色单体交换频率升高、染色体不稳定、DNA损伤增加和对某些遗传毒性应激的更大敏感性。描述RECQ 1催化功能的哪些方面有助于观察到的细胞表型，以及这是如何调节的，这对于建立其在DNA代谢中的生物学功能至关重要。最近的研究已经确定了RECQ 1在DNA修复中的功能特化;然而，确定基本相似性对于开发RecQ行动的统一主题同样重要，允许从研究一个同源物中揭示的功能外推和推广到其他RecQ同源物。
The RecQ helicases are a highly conserved family of DNA-unwinding enzymes that play key roles in protecting the genome stability in all kingdoms of life. Human RecQ homologs include RECQ1, BLM, WRN, RECQ4, and RECQ5β. Although the individual RecQ-related diseases are characterized by a variety of clinical features encompassing growth defects (Bloom Syndrome and Rothmund Thomson Syndrome) to premature aging (Werner Syndrome), all these patients have a high risk of cancer predisposition. Here, we present an overview of recent progress towards elucidating functions of RECQ1 helicase, the most abundant but poorly characterized RecQ homolog in humans. Consistent with a conserved role in genome stability maintenance, deficiency of RECQ1 results in elevated frequency of spontaneous sister chromatid exchanges, chromosomal instability, increased DNA damage and greater sensitivity to certain genotoxic stress. Delineating what aspects of RECQ1 catalytic functions contribute to the observed cellular phenotypes, and how this is regulated is critical to establish its biological functions in DNA metabolism. Recent studies have identified functional specialization of RECQ1 in DNA repair; however, identification of fundamental similarities will be just as critical in developing a unifying theme for RecQ actions, allowing the functions revealed from studying one homolog to be extrapolated and generalized to other RecQ homologs.