A novel mutant allele of Schizosaccharomyces pombe rad26 defective in monitoring S-phase progression to prevent premature mitosis.
A novel mutant allele of Schizosaccharomyces pombe rad26 defective in monitoring S-phase progression to prevent premature mitosis.
复制标题
粟酒裂殖酵母 rad26 的一种新型突变等位基因在监测 S 期进展以防止过早有丝分裂方面存在缺陷。
DOI：
10.1128/mcb.17.6.3103
复制
发表时间：
1997
影响因子：
5.3
通讯作者：
Wang,TS
中科院分区：
文献类型：
--
作者：
Uchiyama,M;Galli,I;Griffiths,DJ;Wang,TS
对一株携带DNA聚合酶δ（polδ ts 03）温敏等位基因的粟酒裂殖酵母（Schizosophyomycespombe）进行了半允许生长条件的研究。在这种情况下，DNA聚合酶δ处于半失活状态，导致S期进展延迟。使用遗传策略，我们已经分离出一组突变体，当DNA复制不完全时，它们进入过早的有丝分裂，但在DNA损伤后，它们在G2/M期的停滞没有缺陷。我们对突变体aya 14进行了鉴定，该突变体在S期被遗传或化学手段阻滞时进入过早的有丝分裂。然而，该突变体对紫外线和γ射线都不敏感。发现两个基因组克隆rad 26+和cds 1+抑制了突变体aya 14对羟基脲的敏感性。遗传分析表明，aya 14是细胞周期检查点26+的一个新等位基因，我们将其命名为rad26.a14。cds 1+是一个抑制因子，当S期被羟基脲或cdc 22抑制时，它抑制frad26.a14的S期反馈控制缺陷，但当S期被突变DNA聚合酶阻滞时，它不抑制缺陷。在多种cdc突变背景中对rad26.a14的分析表明，含有rad26.a14的菌株绕过S期阻滞，但不绕过G1期或晚期S/G2期阻滞。提出了Rad 26如何监测S期进程以维持细胞周期事件的依赖性并与其他rad/huscheckpoint基因产物协调响应辐射损伤的模型。
A semipermissive growth condition was defined for aSchizosaccharomyces pombestrain carrying a thermosensitive allele of DNA polymerase δ (polδts03). Under this condition, DNA polymerase δ is semidisabled and causes a delay in S-phase progression. Using a genetic strategy, we have isolated a panel of mutants that enter premature mitosis when DNA replication is incomplete but which are not defective for arrest in G2/M following DNA damage. We characterized theaya14mutant, which enters premature mitosis when S phase is arrested by genetic or chemical means. However, this mutant is sensitive to neither UV nor gamma irradiation. Two genomic clones,rad26+andcds1+, were found to suppress the hydroxyurea sensitivity of theaya14mutant. Genetic analysis indicates thataya14is a novel allele of the cell cycle checkpoint generad26+, which we have namedrad26.a14. cds1+is a suppressor which suppresses the S-phase feedback control defect ofrad26.a14when S phase is inhibited by either hydroxyurea orcdc22, but it does not suppress the defect when S phase is arrested by a mutant DNA polymerase. Analyses ofrad26.a14in a variety of cdc mutant backgrounds indicate that strains containingrad26.a14bypass S-phase arrest but not G1or late S/G2arrest. A model of howRad26monitors S-phase progression to maintain the dependency of cell cycle events and coordinates with otherrad/huscheckpoint gene products in responding to radiation damage is proposed.