作者
Junko Murai, Sai-Wen Tang, Elisabetta Leo, Simone A Baechler, Christophe E Redon, Hongliang Zhang, Muthana Al Abo, Vinodh N Rajapakse, Eijiro Nakamura, Lisa M Miller Jenkins, Mirit I Aladjem, Yves Pommier
发表日期
2018/2/1
期刊
Molecular cell
卷号
69
期号
3
页码范围
371-384. e6
出版商
Elsevier
简介
SLFN11 sensitizes cancer cells to a broad range of DNA-targeted therapies. Here we show that, in response to replication stress induced by camptothecin, SLFN11 tightly binds chromatin at stressed replication foci via RPA1 together with the replication helicase subunit MCM3. Unlike ATR, SLFN11 neither interferes with the loading of CDC45 and PCNA nor inhibits the initiation of DNA replication but selectively blocks fork progression while inducing chromatin opening across replication initiation sites. The ATPase domain of SLFN11 is required for chromatin opening, replication block, and cell death but not for the tight binding of SLFN11 to chromatin. Replication stress by the CHK1 inhibitor Prexasertib also recruits SLFN11 to nascent replicating DNA together with CDC45 and PCNA. We conclude that SLFN11 is recruited to stressed replication forks carrying extended RPA filaments where it blocks replication by …
学术搜索中的文章
J Murai, SW Tang, E Leo, SA Baechler, CE Redon… - Molecular cell, 2018