CLB5 AND CLB6, A NEW PAIR OF B-CYCLINS INVOLVED IN DNA-REPLICATION IN SACCHAROMYCES-CEREVISIAE

CLB5 AND CLB6, A NEW PAIR OF B-CYCLINS INVOLVED IN DNA-REPLICATION IN SACCHAROMYCES-CEREVISIAE
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DOI:
10.1101/gad.7.7a.1160
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发表时间:
1993-07-01
影响因子:
10.5
通讯作者:
NASMYTH, K
NASMYTH, K
中科院分区:
生物学1区
文献类型:
--
作者:
SCHWOB, E;NASMYTH, K

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酿酒酵母中Cdc28蛋白激酶在DNA复制和有丝分裂中的功能被认为是由与其相关的细胞周期蛋白亚基的类型所决定的。由CLN1、CLN2和CLN3编码的G1期特异性细胞周期蛋白是细胞进入细胞周期(起始点)以及进入S期所必需的,而由CLB1、CLB2、CLB3和CLB4编码的G2期特异性B型细胞周期蛋白是有丝分裂所必需的。我们描述了一个新的B型细胞周期蛋白基因家族,CLB5和CLB6,它们的转录本在G1晚期与CLN1、CLN2以及许多DNA复制所需基因的转录本一同出现。CLB6的缺失影响很小或没有影响,但CLB5的缺失会极大地延长S期,并且两个基因同时缺失会阻止DNA复制的及时启动。CLB5和CLB6的转录通常依赖于Cln的活性,但异位表达CLB5可使细胞在缺乏Cln细胞周期蛋白的情况下增殖。因此,与Clb5/6相关而非与Cln细胞周期蛋白相关的激酶活性可能负责进入S期。Clb5还与Clb3和Clb4一起在有丝分裂纺锤体的形成中发挥作用。我们观察到CLB5参与S期和有丝分裂的起始,这表明一个单一的原始B型细胞周期蛋白可能足以调节许多(如果不是全部)真核生物共同祖先的细胞周期。
The functions of the Cdc28 protein kinase in DNA replication and mitosis in Saccharomyces cerevisiae are thought to be determined by the type of cyclin subunit with which it is associated. G1-specific cyclins encoded by CLN1, CLN2, and CLN3 are required for entry into the cell cycle (Start) and thereby for S phase, whereas G2-specific B-type cyclins encoded by CLB1, CLB2, CLB3, and CLB4 are required for mitosis. We describe a new family of B-type cyclin genes, CLB5 and CLB6, whose transcripts appear in late G1 along with those of CLN1, CLN2, and many genes required for DNA replication. Deletion of CLB6 has little or no effect, but deletion of CLB5 greatly extends S phase, and deleting both genes prevents the timely initiation of DNA replication. Transcription of CLB5 and CLB6 is normally dependent on Cln activity, but ectopic CLB5 expression allows cells to proliferate in the absence of Cln cyclins. Thus, the kinase activity associated with Clb5/6 and not with Cln cyclins may be responsible for S-phase entry. Clb5 also has a function, along with Clb3 and Clb4, in the formation of mitotic spindles. Our observation that CLB5 is involved in the initiation of both S phase and mitosis suggests that a single primordial B-type cyclin might have been sufficient for regulating the cell cycle of the common ancestor of many, if not all, eukaryotes.