Suppressors of cdc25p overexpression identify two pathways that influence the G2/M checkpoint in fission yeast.
Suppressors of cdc25p overexpression identify two pathways that influence the G2/M checkpoint in fission yeast.
复制标题
cdc25p 过度表达的抑制剂确定了影响裂殖酵母中 G2/M 检查点的两条途径。
DOI：
10.1093/genetics/150.4.1361
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发表时间：
1998
期刊：
影响因子：
3.3
通讯作者：
Enoch,T
中科院分区：
文献类型：
--
作者：
Forbes,KC;Humphrey,T;Enoch,T
检查点维持细胞周期事件的顺序。在G2/M，检查点阻断有丝分裂以响应受损或未复制的DNA。对受损DNA和未复制DNA的检查点反应存在显着差异，尽管许多相同的基因参与了这两种反应。为了鉴定在DNA复制检查点途径中特异性发挥功能的新基因，我们寻找了Cdc 25 p（OPcdc 25+）过度产生的高拷贝抑制因子，其缺乏DNA复制检查点。分离出两类抑制因子。一类包括一个新的基因编码一个推定的DEAD盒解旋酶，抑制不受控制的有丝分裂（sum 3+）。该基因负调控细胞周期反应的压力时，过表达和恢复检查点反应的机制是独立的Cdc 2 p酪氨酸磷酸化。第二类包括chk 1+和两个裂殖酵母14-3-3基因，rad 24+和rad 25+，它们似乎通过抑制Cdc 25 p来抑制检查点缺陷。我们发现，rad 24 Δ突变体在37°时对DNA复制抑制剂羟基脲的检查点反应有缺陷，而cds 1 Δ rad 24 Δ突变体，如cds 1 Δ chk 1 Δ突变体，在29°时完全是检查点缺陷。这些结果表明，chk 1+和rad 24+可能与cds 1+在对未复制DNA的检查点反应中冗余地起作用。
Checkpoints maintain the order of cell-cycle events. At G2/M, a checkpoint blocks mitosis in response to damaged or unreplicated DNA. There are significant differences in the checkpoint responses to damaged DNA and unreplicated DNA, although many of the same genes are involved in both responses. To identify new genes that function specifically in the DNA replication checkpoint pathway, we searched for high-copy suppressors of overproducer of Cdc25p (OPcdc25+), which lacks a DNA replication checkpoint. Two classes of suppressors were isolated. One class includes a new gene encoding a putative DEAD box helicase, suppressor of uncontrolled mitosis (sum3+). This gene negatively regulates the cell-cycle response to stress when overexpressed and restores the checkpoint response by a mechanism that is independent of Cdc2p tyrosine phosphorylation. The second class includes chk1+and the two Schizosaccharomyces pombe 14-3-3 genes, rad24+and rad25+, which appear to suppress the checkpoint defect by inhibiting Cdc25p. We show that rad24Δ mutants are defective in the checkpoint response to the DNA replication inhibitor hydroxyurea at 37° and that cds1Δ rad24Δ mutants, like cds1Δ chk1Δ mutants, are entirely checkpoint deficient at 29°. These results suggest that chk1+and rad24+may function redundantly with cds1+in the checkpoint response to unreplicated DNA.