DNA damage induces Yap5-dependent transcription of ECO1/CTF7 in Saccharomyces cerevisiae.
DNA damage induces Yap5-dependent transcription of ECO1/CTF7 in Saccharomyces cerevisiae.
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DOI：
10.1371/journal.pone.0242968
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Skibbens RV
中科院分区：
文献类型：
--
作者：
Mfarej MG;Skibbens RV
酵母Eco 1（人类ESCO 2）乙酰转移酶将染色质结合的粘附素转化为DNA束缚状态，从而建立姐妹染色单体的凝聚力。Eco 1在DNA复制期间建立内聚性，之后Eco 1被SCF E3泛素连接酶靶向降解。SCF E3连接酶和促进Eco 1泛素化和降解的连续磷酸化在整个M期保持活性。这样，Eco 1蛋白水平在S期高，但在整个剩余的细胞周期中保持低水平。然而，在M期DNA损伤的反应中，Eco 1活性增加，提供了新一波的凝聚力建立（称为损伤诱导凝聚力，或DIC），这对有效的DNA修复至关重要。到目前为止，几乎没有证据表明Eco 1活性在M期响应DNA损伤而增加的机制。可能包括靶向Eco 1降解的激酶或E3连接酶在响应DNA损伤时受到抑制。我们的研究结果表明，相反，降解机制仍然完全活跃在M期，尽管存在的DNA损伤。在测试替代模型中，通过该模型Eco 1活性响应于DNA损伤而增加，结果显示DNA损伤诱导Eco 1的新转录，并且以超过Eco 1周转率的速率，提供Eco 1蛋白的快速积累。我们进一步表明，ECO 1转录的DNA损伤诱导部分由Yap 5-胁迫诱导的转录因子调节。鉴于突变的ESCO 2（ECO 1的同源物）在人类出生缺陷中的作用，这项研究强调了ESCO 2突变和ESCO 2调节缺陷的复杂性，可能会促进发育异常并导致包括癌症在内的各种疾病。
Yeast Eco1 (ESCO2 in humans) acetyltransferase converts chromatin-bound cohesins to a DNA tethering state, thereby establishing sister chromatid cohesion. Eco1 establishes cohesion during DNA replication, after which Eco1 is targeted for degradation by SCF E3 ubiquitin ligase. SCF E3 ligase, and sequential phosphorylations that promote Eco1 ubiquitination and degradation, remain active throughout the M phase. In this way, Eco1 protein levels are high during S phase, but remain low throughout the remaining cell cycle. In response to DNA damage during M phase, however, Eco1 activity increases—providing for a new wave of cohesion establishment (termed Damage-Induced Cohesion, or DIC) which is critical for efficient DNA repair. To date, little evidence exists as to the mechanism through which Eco1 activity increases during M phase in response to DNA damage. Possibilities include that either the kinases or E3 ligase, that target Eco1 for degradation, are inhibited in response to DNA damage. Our results reveal instead that the degradation machinery remains fully active during M phase, despite the presence of DNA damage. In testing alternate models through which Eco1 activity increases in response to DNA damage, the results reveal that DNA damage induces new transcription of ECO1 and at a rate that exceeds the rate of Eco1 turnover, providing for rapid accumulation of Eco1 protein. We further show that DNA damage induction of ECO1 transcription is in part regulated by Yap5—a stress-induced transcription factor. Given the role for mutated ESCO2 (homolog of ECO1) in human birth defects, this study highlights the complex nature through which mutation of ESCO2, and defects in ESCO2 regulation, may promote developmental abnormalities and contribute to various diseases including cancer.
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DOI：
10.4161/cc.9.21.13634
发表时间：
2010-11-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Maradeo ME;Garg A;Skibbens RV
通讯作者：
Skibbens RV
影响因子：
10.5
作者：
ELLEDGE, SJ;DAVIS, RW
通讯作者：
DAVIS, RW
影响因子：
2.4
作者：
Banerji R;Skibbens RV;Iovine MK
通讯作者：
Iovine MK
影响因子：
11.4
作者：
Delaunay, A;Isnard, AD;Toledano, MB
通讯作者：
Toledano, MB
影响因子：
3.3
作者：
Guacci V;Koshland D
通讯作者：
Koshland D