Takei Y, Swietlik M, Tanoue A, Tsujimoto G, Kouzarides T, Laskey R
Wellcome/CRC Institute, Cambridge, UK.
EMBO Rep. 2001 Feb;2(2):119-23. doi: 10.1093/embo-reports/kve026.
The MCM proteins are essential for the initiation of DNA replication. We have isolated an MCM3-associated protein (MCM3AP) in a two-hybrid screen using MCM3. Here we demonstrate that MCM3AP is an acetyltransferase which acetylates MCM3 and that chromatin-bound MCM3 is acetylated in vivo. The MCM3 acetylase, MCM3AP, is also chromatin-bound. This study also indicates that MCM3AP contains putative acetyl CoA binding motifs conserved within the GCN5-related N-acetyltransferase superfamily. Mutation of those motifs significantly inhibits the MCM3 acetylase activity. Over-expression of MCM3AP inhibits DNA replication, whereas mutation of the acetylase motifs abolishes this effect, suggesting that acetylation plays a role in DNA replication. Taken together, we suggest that MCM3 acetylation is a novel pathway which might regulate DNA replication.
MCM蛋白对于DNA复制的起始至关重要。我们在使用MCM3进行的双杂交筛选中分离出了一种MCM3相关蛋白(MCM3AP)。在此我们证明MCM3AP是一种使MCM3乙酰化的乙酰转移酶,并且染色质结合的MCM3在体内被乙酰化。MCM3乙酰化酶MCM3AP也与染色质结合。这项研究还表明MCM3AP含有在GCN5相关的N - 乙酰转移酶超家族中保守的假定乙酰辅酶A结合基序。这些基序的突变显著抑制MCM3乙酰化酶活性。MCM3AP的过表达抑制DNA复制,而乙酰化酶基序的突变消除了这种作用,表明乙酰化在DNA复制中起作用。综上所述,我们认为MCM3乙酰化是一条可能调节DNA复制的新途径。