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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis
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Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis

机译：Frag1，替代复制因子C亚基的同源物，将复制应激监测与细胞凋亡联系起来

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摘要

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.
机译：我们报告鉴定和鉴定的基因组完整性，小鼠和人类FRAG1基因，复制因子C大亚基的保守同源物，与替代复制因子C亚基Elg1，Ctf18 / Chl12和Rad24的发芽酵母的保守的同系物的有效调节剂。 。 FRAG1是在寻找与复制压力条件下调节基因组稳定性有关的关键看守基因中发现的。响应压力，Atr参与下调FRAG1表达，从而通过在细胞周期S期从受损染色质释放Rac9来诱导凋亡，从而使Rad9-Bcl2缔合并诱导凋亡的Bax蛋白。我们建议Frag1信号通路，通过将复制压力监测与凋亡诱导联系起来，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方面起着核心作用。

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