Masai Hisao, Yang Chi-Chun, Matsumoto Seiji
Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
Curr Genet. 2017 Oct;63(5):813-818. doi: 10.1007/s00294-017-0690-y. Epub 2017 Mar 29.
Mrc1 and its vertebrate homologue Claspin serve as a mediator for replication stress checkpoint signaling, receiving the signal from Mec1/Rad3/ATR sensor kinase and transmitting it to the effector Rad53/Cds1/Chk1 kinase. They are likely to be a part of the replisome and facilitate the S-phase progression by promoting replication fork progression. Recent reports on Mrc1/Claspin indicate their new role in regulating the replication initiation through interaction with Cdc7, a key conserved serine-threonine kinase that triggers firing at each replication origin. Mrc1/Claspin has a specific domain that specifically interacts with Cdc7, and this domain is involved also in intramolecular interaction with its N-terminal segment. Mechanisms for novel regulation of origin firing and its timing through recruitment of Cdc7 to Mrc1/Claspin will be discussed.
Mrc1及其脊椎动物同源物Claspin作为复制应激检查点信号的介质，接收来自Mec1/Rad3/ATR传感激酶的信号并将其传递给效应器Rad53/Cds1/Chk1激酶。它们可能是复制体的一部分，并通过促进复制叉的进展来促进S期进程。最近关于Mrc1/Claspin的报道表明它们在通过与Cdc7相互作用调节复制起始方面的新作用，Cdc7是一种关键的保守丝氨酸 - 苏氨酸激酶，可在每个复制起点触发起始。Mrc1/Claspin有一个与Cdc7特异性相互作用的特定结构域，该结构域也参与与其N端片段的分子内相互作用。将讨论通过将Cdc7招募到Mrc1/Claspin来对起始点激发及其时间进行新调控的机制。
