Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis
Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis
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DOI：
10.1073/pnas.0504222102
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发表时间：
2005-07-05
影响因子：
11.1
通讯作者：
Furukawa, Y
中科院分区：
文献类型：
--
作者：
Ishii, H;Inageta, T;Furukawa, Y
我们报告了一个有效的基因组完整性，小鼠和人类FRAG 1基因，复制因子C大亚基，是同源的替代复制因子C亚基Elg 1，Ctf 18/Chl 12，和Rad 24的芽殖酵母的一个保守的同源物的调节器的鉴定和表征。FRAG 1是在寻找复制应激条件下参与基因组稳定性调节的关键看守基因中鉴定的。在应激反应中，Atr参与FRAG 1表达的下调，导致在细胞周期的S期期间通过从受损的染色质释放Rac 9诱导细胞凋亡，允许Rad 9-Bcl 2缔合和诱导促凋亡Bax蛋白。我们建议，Frag 1信号通路，通过连接复制应激监视与凋亡诱导，在确定DNA损伤是否与细胞存活相容或是否需要通过凋亡消除细胞中起着核心作用。
We report the identification and characterization of a potent regulator of genomic integrity, mouse and human FRAG1 gene, a conserved homolog of replication factor C large subunit that is homologous to the alternative replication factor C subunits Elg1, Ctf18/Chl12, and Rad24 of budding yeast. FRAG1 was identified in a search for key caretaker genes involved in the regulation of genomic stability under conditions of replicative stress. In response to stress, Atr participates in the down-regulation of FRAG1 expression, leading to the induction of apoptosis through the release of Rac9 from damaged chromatin during the S phase of the cell cycle, allowing Rad9-Bcl2 association and induction of proapoptotic Bax protein. We propose that the Frag1 signal pathway, by linking replication stress surveillance with apoptosis induction, plays a central role in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis.