DNA引发酶在将DNA复制与DNA损伤反应相偶联中的作用。
A role for DNA primase in coupling DNA replication to DNA damage response.
作者信息
Marini F, Pellicioli A, Paciotti V, Lucchini G, Plevani P, Stern D F, Foiani M
机构信息
Dipartimento di Genetica e di Biologia dei Microrganismi, Università degli Studi di Milano, Italy.
出版信息
EMBO J. 1997 Feb 3;16(3):639-50. doi: 10.1093/emboj/16.3.639.
Abstract
The temperature-sensitive yeast DNA primase mutant pri1-M4 fails to execute an early step of DNA replication and exhibits a dominant, allele-specific sensitivity to DNA-damaging agents. pri1-M4 is defective in slowing down the rate of S phase progression and partially delaying the G1-S transition in response to DNA damage. Conversely, the G2 DNA damage response and the S-M checkpoint coupling completion of DNA replication to mitosis are unaffected. The signal transduction pathway leading to Rad53p phosphorylation induced by DNA damage is proficient in pri1-M4, and cell cycle delay caused by Rad53p overexpression is counteracted by the pri1-M4 mutation. Altogether, our results suggest that DNA primase plays an essential role in a subset of the Rad53p-dependent checkpoint pathways controlling cell cycle progression in response to DNA damage.
摘要
温度敏感型酵母DNA引发酶突变体pri1-M4无法执行DNA复制的早期步骤，并且对DNA损伤剂表现出显性的、等位基因特异性的敏感性。pri1-M4在减缓S期进程速率以及响应DNA损伤而部分延迟G1-S转换方面存在缺陷。相反，G2期DNA损伤反应以及将DNA复制完成与有丝分裂相偶联的S-M检查点未受影响。由DNA损伤诱导导致Rad53p磷酸化的信号转导途径在pri1-M4中功能正常，并且由Rad53p过表达引起的细胞周期延迟可被pri1-M4突变抵消。总之，我们的结果表明，DNA引发酶在响应DNA损伤控制细胞周期进程的一部分Rad53p依赖性检查点途径中起重要作用。
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