Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells.
Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells.
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DOI：
10.18632/oncotarget.6342
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发表时间：
2015-12-01
期刊：
影响因子：
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通讯作者：
Hickson ID
中科院分区：
文献类型：
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作者：
Kliszczak M;Sedlackova H;Pitchai GP;Streicher WW;Krejci L;Hickson ID
DNA复制是一个高度协调的过程，在真核生物中从多个复制起点开始。这些起点被起点识别复合物（ORC）结合，随后以Cdt 1/Cdc 6依赖的方式招募Mcm 2 -7复制解旋酶。在芽殖酵母中，两个基本的复制因子Sld 2和Mcm 10对于复制起点的激活是重要的。在人类中，推定的Sld 2同源物RECQ 4与MCM 10相互作用。在这里，我们已经鉴定了两种与MCM 10结合缺陷的人RECQ 4突变体。我们表明，这些RECQ 4变体能够补充禽类细胞RECQ 4缺失突变体的致死性，表明RECQ 4在脊椎动物中的基本功能不太可能需要与MCM 10结合。然而，我们发现RECQ 4-MCM 10相互作用对于有效的复制起点发射是重要的。
DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing.