Enomoto T
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
J Biochem. 2001 Apr;129(4):501-7. doi: 10.1093/oxfordjournals.jbchem.a002883.
Escherichia coli RecQ helicase is a component of the RecF pathway of recombination whose components are required to reassemble a replisome complex at the site of the replication fork after the removal of a lesion. There are at least five RecQ homologues in human cells, including BLM and WRN. The genes encoding BLM and WRN are mutated in the cancer-prone disorder Bloom's syndrome (BS) and the plogeroid disorder Werner's syndrome (WS), respectively. These syndromes are characterized by a high degree of genomic instability, including chromosomal breaks, multiple large deletions, and translocations, and cells derived from BS and WS patients show defects in DNA replication. Recently, it has become clear that a Holliday junction-like structure is formed at stalled replication forks to result in the formation of double-stranded breaks, and recombination plays an important role in the repair of stalled or broken replication forks, leading to the reinitiation of replication. Defects in the processing of stalled replication forks could lead to aberrant recombination events resulting in genetic instability. Recent studies on BLM, WRN, and the RecQ homologue of Saccharomyces cerevisiae, Sgs1, indicate that these RecQ homologues interact with proteins involved in DNA replication, and function in a pathway from the DNA replication check point to homologous recombination.
大肠杆菌RecQ解旋酶是重组RecF途径的一个组成部分,该途径的组成成分在去除损伤后需要在复制叉位点重新组装复制体复合物。人类细胞中至少有五种RecQ同源物,包括BLM和WRN。编码BLM和WRN的基因分别在易患癌症的布卢姆综合征(BS)和类早老症沃纳综合征(WS)中发生突变。这些综合征的特征是高度的基因组不稳定,包括染色体断裂、多个大的缺失和易位,并且来自BS和WS患者的细胞在DNA复制中表现出缺陷。最近,已经清楚的是,在停滞的复制叉处会形成类似霍利迪连接体的结构,从而导致双链断裂的形成,并且重组在停滞或断裂的复制叉的修复中起重要作用,导致复制的重新起始。停滞的复制叉处理缺陷可能导致异常的重组事件,从而导致遗传不稳定。最近对BLM、WRN以及酿酒酵母的RecQ同源物Sgs1的研究表明,这些RecQ同源物与参与DNA复制的蛋白质相互作用,并在从DNA复制检查点到同源重组的途径中发挥作用。