酵母Mrc1基因是多細(xì)胞動(dòng)物Claspin的一種同源基因（ortholog）,，Mrc1基因不但是正常的DNA復(fù)制叉（replication fork）的一個(gè)中心組成部分，同時(shí)也是S期檢查點(diǎn)的一個(gè)重要調(diào)節(jié)子,。在2008年10月10日出版的《分子細(xì)胞》（Molecular Cell）上,，來自美國和日本的一組科學(xué)家發(fā)表文章稱他們發(fā)現(xiàn)Mrc1能通過與DNA聚合酶共同作用,，從而影響DNA的復(fù)制。
在封面文章中,，研究人員發(fā)現(xiàn)Mrc1能夠與Pol2發(fā)生相互作用,，Pol2是DNA聚合酶ε的一個(gè)催化亞基，它們對(duì)于DNA領(lǐng)頭鏈（leading strand）的復(fù)制以及檢查點(diǎn)都非常重要,。Mrc1能分別與細(xì)胞中Pol2的氨基末端（Pol2N）和羧基末端部分（Pol2C）發(fā)生作用,。令人驚訝的是,，在S期檢查點(diǎn)時(shí)期發(fā)生的Mrc1磷酸化過程將會(huì)去除與Pol2N的結(jié)合發(fā)生，但是卻不會(huì)影響到與Pol2C的相互作用,。Mrc1對(duì)于HU蛋白復(fù)制叉Pol2的穩(wěn)定是必需的,。對(duì)于野生型細(xì)胞，S期檢查點(diǎn)保證了在存在復(fù)制抑制劑-羥基脲（hydroxyurea）的情況下,，DNA復(fù)制蛋白依然與復(fù)制叉關(guān)聯(lián),。在缺少M(fèi)rc1時(shí)，大部分蛋白仍然位于復(fù)制叉上,，然而此時(shí)Pol2則完全分離了,。
因此科學(xué)家們認(rèn)為，這種獨(dú)特的Mrc1/ Pol2雙向相互作用或許是在發(fā)生了領(lǐng)頭鏈的DNA破壞情況下調(diào)節(jié)S期檢查點(diǎn)的一個(gè)額外步驟,。作者在文章中表示,，同時(shí)還能與MCMs發(fā)生作用的Mrc1或許起到調(diào)節(jié)復(fù)制叉的聚合與分離等的作用。（生物谷Bioon.com）
生物谷推薦原始出處：
Molecular Cell,，Vol 32, 106-117, 10 October 2008,，Huiqiang Lou, Judith L. Campbell
Mrc1 and DNA Polymerase ε Function Together in Linking DNA Replication and the S Phase Checkpoint
Huiqiang Lou,1 Makiko Komata,2 Yuki Katou,2 Zhiyun Guan,1 Clara C. Reis,1 Martin Budd,1 Katsuhiko Shirahige,2 and Judith L. Campbell1,
1 Braun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA
2 Laboratory of Genome Structure and Function, Division for Gene Research, Center for Biological Resources and Informatics, Tokyo Institute of Technology, B-65, 4259, Nagatsuta, Midori-ku, Yokohama City, Kanagawa 226-8501, Japan
Summary
Yeast Mrc1, ortholog of metazoan Claspin, is both a central component of normal DNA replication forks and a mediator of the S phase checkpoint. We report that Mrc1 interacts with Pol2, the catalytic subunit of DNA polymerase ε, essential for leading-strand DNA replication and for the checkpoint. In unperturbed cells, Mrc1 interacts independently with both the N-terminal and C-terminal halves of Pol2 (Pol2N and Pol2C). Strikingly, phosphorylation of Mrc1 during the S phase checkpoint abolishes Pol2N binding, but not Pol2C interaction. Mrc1 is required to stabilize Pol2 at replication forks stalled in HU. The bimodal Mrc1/Pol2 interaction may be an additional step in regulating the S phase checkpoint response to DNA damage on the leading strand. We propose that Mrc1, which also interacts with the MCMs, may modulate coupling of polymerization and unwinding at the replication fork.
