Verkade H M, O'Connell M J
Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne VIC, Australia.
Mol Gen Genet. 1998 Dec;260(5):426-33. doi: 10.1007/s004380050913.
A checkpoint responding to DNA damage in G2 results in a delay in the onset of mitosis through inhibition of p34cdc2 kinase activity via maintenance of inhibitory tyrosine phosphorylation. Genetic analyses of this checkpoint in fission yeast have identified single alleles of several genes, suggesting these screens are not yet saturating, and hence further genes await identification. To fully understand the complexity of this checkpoint it will be necessary to define all the genes involved. To this end we screened for new mutants defective in the ability to delay mitosis in the presence of DNA-damaging agents. Twenty-four mutants were isolated that were defective in UV-C and MMS-induced checkpoint delay. Amongst these mutants was an allele of cut5 that was also defective in the checkpoint responses. We show here, contrary to previous reports, that the UV-C induced checkpoint response is defective in cut5 mutants. Therefore, like all other checkpoint mutants, cut5 is required for G2 checkpoint arrest following DNA damage, regardless of the nature of the lesions involved.
一个在G2期对DNA损伤作出反应的关卡，通过维持抑制性酪氨酸磷酸化来抑制p34cdc2激酶活性，从而导致有丝分裂起始延迟。对裂殖酵母中这个关卡的遗传学分析已经鉴定出几个基因的单个等位基因，这表明这些筛选尚未饱和，因此还有更多基因有待鉴定。为了全面理解这个关卡的复杂性，有必要确定所有涉及的基因。为此，我们筛选了在存在DNA损伤剂时延迟有丝分裂能力有缺陷的新突变体。分离出了24个在UV-C和MMS诱导的关卡延迟方面有缺陷的突变体。在这些突变体中，有一个cut5等位基因在关卡反应中也有缺陷。我们在此表明，与之前的报道相反，UV-C诱导的关卡反应在cut5突变体中是有缺陷的。因此，与所有其他关卡突变体一样，无论所涉及损伤的性质如何，DNA损伤后G2关卡阻滞都需要cut5。
