Suski Catherine, Marians Kenneth J
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Mol Cell. 2008 Jun 20;30(6):779-89. doi: 10.1016/j.molcel.2008.04.020.
RecQ-like DNA helicases pair with cognate topoisomerase III enzymes to function in the maintenance of genomic integrity in many organisms. These proteins play roles in stabilizing stalled replication forks, the S phase checkpoint response, and suppressing genetic crossovers, and their inactivation results in hyper-recombination, gross chromosomal rearrangements, chromosome segregation defects, and human disease. Biochemical activities associated with these enzymes include the ability to resolve double Holliday junctions, a process thought to lead to the suppression of crossover formation. Using Escherichia coli RecQ and topoisomerase III, we demonstrate a second activity for this pair of enzymes that could account for their role in maintaining genomic stability: resolution of converging replication forks. This resolution reaction is specific for the RecQ-topoisomerase III pair and is mediated by interaction of both of these enzymes with the single-stranded DNA-binding protein SSB.
类RecQ DNA解旋酶与同源拓扑异构酶III结合,在许多生物体中维持基因组完整性方面发挥作用。这些蛋白质在稳定停滞的复制叉、S期检查点反应以及抑制基因交换中发挥作用,它们的失活会导致超重组、大规模染色体重排、染色体分离缺陷以及人类疾病。与这些酶相关的生化活性包括解决双Holliday连接的能力,这一过程被认为会导致交叉形成的抑制。利用大肠杆菌RecQ和拓扑异构酶III,我们证明了这对酶的第二种活性,这可以解释它们在维持基因组稳定性中的作用:解决汇聚的复制叉。这种解决反应对RecQ-拓扑异构酶III对具有特异性,并且由这两种酶与单链DNA结合蛋白SSB的相互作用介导。