Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon K Y, Hurwitz J, Yatagai F, Hanaoka F
Division of Radioisotope Technology, Cellular Physiology Laboratory, RIKEN (The Institute of Physical and Chemical Research), Wako, Saitama 351-0198, Japan.
Nucleic Acids Res. 2000 Dec 1;28(23):4769-77. doi: 10.1093/nar/28.23.4769.
Mcm10 (Dna43), first identified in Saccharomyces cerevisiae, is an essential protein which functions in the initiation of DNA synthesis. Mcm10 is a nuclear protein that is localized to replication origins and mediates the interaction of the Mcm2-7 complex with replication origins. We identified and cloned a human cDNA whose product was structurally homologous to the yeast Mcm10 protein. Human Mcm10 (HsMcm10) is a 98-kDa protein of 874 amino acids which shows 23 and 21% overall similarity to Schizosaccharomyces pombe Cdc23 and S. cerevisiae Mcm10, respectively. The messenger RNA level of HsMcm10 increased at the G(1)/S-boundary when quiescent human NB1-RGB cells were induced to proliferate as is the case of many replication factors. HsMcm10 associated with nuclease-resistant nuclear structures throughout S phase and dissociated from it in G(2) phase. HsMcm10 associated with human Orc2 protein when overexpressed in COS-1 cells. HsMcm10 also interacted with Orc2, Mcm2 and Mcm6 proteins in the yeast two-hybrid system. These results suggest that HsMcm10 may function in DNA replication through the interaction with Orc and Mcm2-7 complexes.
Mcm10（Dna43）最初是在酿酒酵母中被鉴定出来的，是一种在DNA合成起始过程中发挥作用的必需蛋白。Mcm10是一种核蛋白，定位于复制起点，并介导Mcm2 - 7复合物与复制起点的相互作用。我们鉴定并克隆了一个人类cDNA，其产物在结构上与酵母Mcm10蛋白同源。人类Mcm10（HsMcm10）是一种由874个氨基酸组成的98 kDa蛋白，与粟酒裂殖酵母Cdc23和酿酒酵母Mcm10的总体相似性分别为23%和21%。与许多复制因子一样，当静止的人类NB1 - RGB细胞被诱导增殖时，HsMcm10的信使RNA水平在G(1)/S边界处升高。HsMcm10在整个S期与抗核酸酶的核结构相关联，并在G(2)期与之解离。当在COS - 1细胞中过表达时，HsMcm10与人类Orc2蛋白相关联。在酵母双杂交系统中，HsMcm10还与Orc2、Mcm2和Mcm6蛋白相互作用。这些结果表明，HsMcm10可能通过与Orc和Mcm2 - 7复合物相互作用在DNA复制中发挥作用。
