The DNA replication checkpoint directly regulates MBF-dependent G1/S transcription
The DNA replication checkpoint directly regulates MBF-dependent G1/S transcription
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DOI：
10.1128/mcb.00596-08
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发表时间：
2008-10-01
影响因子：
5.3
通讯作者：
Rhind, Nicholas
中科院分区：
文献类型：
--
作者：
Dutta, Chaitali;Patel, Prasanta K.;Rhind, Nicholas
DNA复制检查点在转录上上调基因，使细胞能够适应复制应激并存活下来。我们的研究结果表明，在裂殖酵母裂殖酵母中，复制检查点通过直接调节MBF（G（1）/S转录因子）来调节整个G（1）/S转录程序。复制检查点不是启动检查点特异性转录程序，而是靶向MBF以在复制应激期间维持正常的G（1）/S转录程序。我们提出了一种机制，这种调节的基础上，在体外磷酸化的Cdc 10亚基MBF的Cds 1复制检查点激酶。两个潜在的磷酸化位点与磷酸化模拟氨基酸的替代足以促进检查点转录程序，这表明Cds 1磷酸化直接调节MBF依赖的转录。裂殖酵母和芽殖酵母之间MBF的保守性，以及最近的结果暗示MBF作为芽殖酵母复制检查点的靶点，表明MBF转录因子的检查点调节是应对复制应激的保守策略。此外，MBF和E2 F（后生动物G（1）/S转录因子）之间的结构和调控相似性表明，这种检查点机制可能在真核生物中广泛保守。
The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G(1)/S transcriptional program by directly regulating MBF, the G(1)/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G(1)/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitro phosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Replacement of two potential phosphorylation sites with phosphomimetic amino acids suffices to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggests that checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G(1)/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes.