title: Mrc1/Claspin: a new role for regulation of origin firing.
abstract: 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.
authors.affiliation: Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. masai-hs@igakuken.or.jp.
authors.forename: Hisao
authors.initials: H
authors.lastname: Masai
authors.affiliation: Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Chi-Chun
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsumoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D004261:DNA Replication; D006801:Humans; D008322:Mammals; D008562:Membrane Glycoproteins; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018741:Replication Origin; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C488158:CLSPN protein, human; D018797:Cell Cycle Proteins; C573543:MRC1 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C068619:CDC7 protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C021370:homoserine kinase; D017346:Protein Serine-Threonine Kinases
keywords: Cdc7 kinase; Claspin; Intramolecular interaction; Mrc1; Origin firing; Replication timing