Nordea Center for Healthy Ageing, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200N, Copenhagen, Denmark.
Adv Exp Med Biol. 2013;767:161-84. doi: 10.1007/978-1-4614-5037-5_8.
The RecQ family of DNA helicases is highly conserved throughout -evolution, and is important for the maintenance of genome stability. In humans, five RecQ family members have been identified: BLM, WRN, RECQ4, RECQ1 and RECQ5. Defects in three of these give rise to Bloom's syndrome (BLM), Werner's syndrome (WRN) and Rothmund-Thomson/RAPADILINO/Baller-Gerold (RECQ4) syndromes. These syndromes are characterised by cancer predisposition and/or premature ageing. In this review, we focus on the roles of BLM and its S. cerevisiae homologue, Sgs1, in genome maintenance. BLM/Sgs1 has been shown to play a critical role in homologous recombination at multiple steps, including end-resection, displacement loop formation, branch migration and double Holliday junction dissolution. In addition, recent evidence has revealed a role for BLM/Sgs1 in the stabilisation and repair of replication forks damaged during a perturbed S-phase. Finally BLM also plays a role in the suppression and/or resolution of ultra-fine anaphase DNA bridges that form between sister-chromatids during mitosis.
RecQ 家族的 DNA 解旋酶在整个进化过程中高度保守,对维持基因组稳定性至关重要。在人类中,已经鉴定出 5 种 RecQ 家族成员:BLM、WRN、RECQ4、RECQ1 和 RECQ5。其中 3 种缺陷会导致布卢姆综合征(BLM)、沃纳综合征(WRN)和罗氏综合征(RECQ4)。这些综合征的特征是易患癌症和/或早衰。在这篇综述中,我们重点介绍 BLM 及其酿酒酵母同源物 Sgs1 在基因组维持中的作用。BLM/Sgs1 已被证明在多个步骤中的同源重组中发挥关键作用,包括末端切除、位移环形成、分支迁移和双 Holliday 结溶解。此外,最近的证据表明 BLM/Sgs1 在稳定和修复受到干扰的 S 期复制叉方面发挥作用。最后,BLM 还在抑制和/或解决有丝分裂过程中姐妹染色单体之间形成的超微后期 DNA 桥方面发挥作用。