Sami Furqan, Sharma Sudha
Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, 520 W Street, NW, Washington, DC 20059, USA.
Comput Struct Biotechnol J. 2013 Oct 18;6:e201303014. doi: 10.5936/csbj.201303014. eCollection 2013.
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.
RecQ解旋酶是一类高度保守的DNA解旋酶家族，在保护所有生命王国的基因组稳定性方面发挥着关键作用。人类RecQ同源物包括RECQ1、BLM、WRN、RECQ4和RECQ5β。尽管个体RecQ相关疾病具有多种临床特征，从生长缺陷（布卢姆综合征和罗思蒙德-汤姆森综合征）到早衰（沃纳综合征），但所有这些患者都有很高的癌症易感性风险。在这里，我们概述了在阐明RECQ1解旋酶功能方面的最新进展，RECQ1是人类中含量最丰富但特征描述较少的RecQ同源物。与在维持基因组稳定性方面的保守作用一致，RECQ1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损伤增加以及对某些基因毒性应激的敏感性增加。确定RECQ1催化功能的哪些方面导致了观察到的细胞表型，以及其如何被调节对于确定其在DNA代谢中的生物学功能至关重要。最近的研究已经确定了RECQ1在DNA修复中的功能特化；然而，识别基本相似性对于形成RecQ作用的统一主题同样至关重要，这使得从研究一个同源物中揭示的功能能够外推并推广到其他RecQ同源物。
