Osman Fekret, Whitby Matthew C
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
DNA Repair (Amst). 2007 Jul 1;6(7):1004-17. doi: 10.1016/j.dnarep.2007.02.019. Epub 2007 Apr 3.
Cells of all living organisms have evolved complex mechanisms that serve to stabilise, repair and restart stalled, blocked and broken replication forks. The heterodimeric Mus81-Eme1/Mms4 structure-specific endonuclease appears to play an important role(s) in homologous recombination-mediated processing of such perturbed forks. This enzyme has been implicated in the cleavage of stalled and blocked replication forks to initiate recombination, as well as in the processing of recombination intermediates that result from repairing damaged forks. In this review we assess the biochemical and genetic evidence for the mitotic role of Mus81-Eme1/Mms4 at replication forks and in repairing post-replication DNA damage. Mus81 appears to act when replication is impeded by genotoxins or by impairment of the replication machinery, or when arrested replication forks are not adequately protected. We discuss how its action is regulated by the S-phase cell cycle checkpoint, depending on the nature of the stalled or damaged fork. We also present a new way in which Mus81 may limit crossing over during the repair of post-replication gaps, and explore Mus81's interplay with other components of the recombination machinery, including the RecQ helicases that also play important roles in processing replication and recombination intermediates.
所有生物的细胞都进化出了复杂的机制，用于稳定、修复和重启停滞、受阻及断裂的复制叉。异二聚体Mus81-Eme1/Mms4结构特异性核酸内切酶似乎在同源重组介导的此类受扰复制叉的加工过程中发挥着重要作用。该酶与切割停滞和受阻的复制叉以启动重组有关，也参与了修复受损复制叉产生的重组中间体的加工过程。在本综述中，我们评估了Mus81-Eme1/Mms4在复制叉处的有丝分裂作用以及在修复复制后DNA损伤方面的生化和遗传学证据。当复制受到基因毒素或复制机制受损的阻碍，或者当停滞的复制叉没有得到充分保护时，Mus81似乎会发挥作用。我们讨论了其作用如何根据停滞或受损复制叉的性质，受S期细胞周期检查点的调控。我们还提出了一种Mus81可能在复制后缺口修复过程中限制交叉互换的新方式，并探讨了Mus81与重组机制其他组分的相互作用，包括在加工复制和重组中间体中也发挥重要作用的RecQ解旋酶。
