Mcm10 regulates the stability and chromatin association of DNA polymerase-α
Mcm10 regulates the stability and chromatin association of DNA polymerase-α
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DOI：
10.1016/j.molcel.2004.09.017
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发表时间：
2004-10-22
期刊：
影响因子：
16
通讯作者：
Bielinsky, AK
中科院分区：
文献类型：
--
作者：
Ricke, RM;Bielinsky, AK
Mcm 10是一个保守的真核生物DNA复制因子，其功能至今仍不清楚。我们在这里报告，Mcm 10结合到芽殖酵母的复制起点是细胞周期调节和依赖于推定的解旋酶，Mcm 2 -7。mcm 10也是复制叉的一个重要组件。Mcm 10的一部分结合DNA，如组蛋白缔合测定所示，其允许在体内研究染色质结合。然而，Mcm 10也需要维持DNA聚合酶-α（polalpha）的稳态水平。在温度敏感的mcm 10-td突变体中，在S期耗尽Mcm 10导致polalpha的催化亚基降解，而不影响其他叉组件，如Cdc 45。我们建议，Mcm 10稳定polalpha和招聘复杂的复制起点。在延伸过程中，Mcm 10是复制叉处pola存在所必需的，并且可以通过Mcm 2 -7复合物协调DNA合成与DNA解旋。
Mcm10 is a conserved eukaryotic DNA replication factor whose function has remained elusive. We report here that Mcm10 binding to replication origins in budding yeast is cell cycle regulated and dependent on the putative helicase, Mcm2-7. Mcm10 is also an essential component of the replication fork. A fraction of Mcm10 binds to DNA, as shown by histone association assays that allow for the study of chromatin binding in vivo. However, Mcm10 is also required to maintain steady-state levels of DNA polymerase-alpha (polalpha). In temperature-sensitive mcm10-td mutants, depletion of Mcm10 during S phase results in degradation of the catalytic subunit of polalpha, without affecting other fork components such as Cdc45. We propose that Mcm10 stabilizes polalpha and recruits the complex to replication origins. During elongation, Mcm10 is required for the presence of pola at replication forks and may coordinate DNA synthesis with DNA unwinding by the Mcm2-7 complex.