从DNA复制应激中恢复是S期检查点通路的基本功能。
Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway.
作者信息
Desany B A, Alcasabas A A, Bachant J B, Elledge S J
机构信息
Verna and Marrs McLean Department of Biochemistry, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030 USA.
出版信息
Genes Dev. 1998 Sep 15;12(18):2956-70. doi: 10.1101/gad.12.18.2956.
Abstract
RAD53 and MEC1 are essential genes required for the transcriptional and cell cycle responses to DNA damage and DNA replication blocks. We have examined the essential function of these genes and found that their lethality but not their checkpoint defects can be suppressed by increased expression of genes encoding ribonucleotide reductase. Analysis of viable null alleles revealed that Mec1 plays a greater role in response to inhibition of DNA synthesis than Rad53. The loss of survival in mec1 and rad53 null or point mutants in response to transient inhibition of DNA synthesis is not a result of inappropriate anaphase entry but primarily to an inability to complete chromosome replication. We propose that this checkpoint pathway plays an important role in the maintenance of DNA synthetic capabilities when DNA replication is stressed.
摘要
RAD53和MEC1是DNA损伤和DNA复制受阻时转录和细胞周期反应所需的必需基因。我们研究了这些基因的基本功能，发现编码核糖核苷酸还原酶的基因表达增加可以抑制它们的致死性，但不能抑制其检查点缺陷。对存活的无效等位基因的分析表明，Mec1在对DNA合成抑制的反应中比Rad53发挥更大的作用。mec1和rad53无效或点突变体在DNA合成短暂抑制后存活率的丧失不是由于后期进入不当，而是主要由于无法完成染色体复制。我们提出，当DNA复制受到压力时，这种检查点途径在维持DNA合成能力方面起着重要作用。
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本文引用的文献
1
A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication.一种依赖Mec1和Rad53的检查点控制DNA复制的晚期起始点。
Nature. 1998 Oct 8;395(6702):615-8. doi: 10.1038/27001.
2
S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe.Cds1激酶的S期特异性激活定义了粟酒裂殖酵母中检查点反应的一个子途径。
Genes Dev. 1998 Feb 1;12(3):382-95. doi: 10.1101/gad.12.3.382.
3
Atm-dependent interactions of a mammalian chk1 homolog with meiotic chromosomes.一种哺乳动物chk1同源物与减数分裂染色体的Atm依赖性相互作用。
Curr Biol. 1997 Dec 1;7(12):977-86. doi: 10.1016/s0960-9822(06)00417-9.
4
Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae.酿酒酵母中编码核糖核苷酸还原酶第二个必需小亚基的RNR4的鉴定。
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5
Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216.有丝分裂和G2期检查点控制：丝氨酸216位点Cdc25C磷酸化对14-3-3蛋白结合的调节作用
Science. 1997 Sep 5;277(5331):1501-5. doi: 10.1126/science.277.5331.1501.
6
Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25.哺乳动物中Chk1检查点通路的保守性：通过Cdc25将DNA损伤与细胞周期蛋白依赖性激酶调控联系起来。
Science. 1997 Sep 5;277(5331):1497-501. doi: 10.1126/science.277.5331.1497.
7
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8
Reconstitution of a MEC1-independent checkpoint in yeast by expression of a novel human fork head cDNA.通过表达一种新型人类叉头cDNA在酵母中重建不依赖MEC1的检查点。
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9
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10
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