Roberts Tania M, Zaidi Iram Waris, Vaisica Jessica A, Peter Matthias, Brown Grant W
Department of Biochemistry and Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Mol Biol Cell. 2008 Jan;19(1):171-80. doi: 10.1091/mbc.e07-09-0961. Epub 2007 Oct 31.
RTT107 (ESC4, YHR154W) encodes a BRCA1 C-terminal domain protein that is important for recovery from DNA damage during S phase. Rtt107 is a substrate of the checkpoint kinase Mec1, and it forms complexes with DNA repair enzymes, including the nuclease subunit Slx4, but the role of Rtt107 in the DNA damage response remains unclear. We find that Rtt107 interacts with chromatin when cells are treated with compounds that cause replication forks to arrest. This damage-dependent chromatin binding requires the acetyltransferase Rtt109, but it does not require acetylation of the known Rtt109 target, histone H3-K56. Chromatin binding of Rtt107 also requires the cullin Rtt101, which seems to play a direct role in Rtt107 recruitment, because the two proteins are found in complex with each other. Finally, we provide evidence that Rtt107 is bound at or near stalled replication forks in vivo. Together, these results indicate that Rtt109, Rtt101, and Rtt107, which genetic evidence suggests are functionally related, form a DNA damage response pathway that recruits Rtt107 complexes to damaged or stalled replication forks.
RTT107（ESC4，YHR154W）编码一种BRCA1 C末端结构域蛋白，该蛋白对于S期DNA损伤修复很重要。Rtt107是检查点激酶Mec1的底物，它与包括核酸酶亚基Slx4在内的DNA修复酶形成复合物，但Rtt107在DNA损伤反应中的作用仍不清楚。我们发现，当用导致复制叉停滞的化合物处理细胞时，Rtt107与染色质相互作用。这种损伤依赖性染色质结合需要乙酰转移酶Rtt109，但不需要已知的Rtt109靶标组蛋白H3-K56的乙酰化。Rtt107的染色质结合还需要cullin蛋白Rtt101，它似乎在Rtt107的募集过程中起直接作用，因为这两种蛋白相互结合形成复合物。最后，我们提供证据表明Rtt107在体内结合于停滞的复制叉处或其附近。总之，这些结果表明，遗传证据表明功能相关的Rtt109、Rtt101和Rtt107形成了一条DNA损伤反应途径，该途径将Rtt107复合物募集到受损或停滞的复制叉处。
