The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor.
The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor.
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DOI：
10.1091/mbc.e13-05-0257
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发表时间：
2013-11
影响因子：
3.3
通讯作者：
Ayté J
中科院分区：
文献类型：
--
作者：
Ivanova T;Alves-Rodrigues I;Gómez-Escoda B;Dutta C;DeCaprio JA;Rhind N;Hidalgo E;Ayté J
DNA damage and DNA replication checkpoints regulate differently the G1-to-S phase transcriptional program, resulting in the repression or induction, respectively, of the same set of genes. When this signaling is disrupted, cells are unable to cope with DNA-damaging agents, leading to increased cell lethality. In fission yeast cells, Cds1 is the effector kinase of the DNA replication checkpoint. We previously showed that when the DNA replication checkpoint is activated, the repressor Yox1 is phosphorylated and inactivated by Cds1, resulting in activation of MluI-binding factor (MBF)–dependent transcription. This is essential to reinitiate DNA synthesis and for correct G1-to-S transition. Here we show that Cdc10, which is an essential part of the MBF core, is the target of the DNA damage checkpoint. When fission yeast cells are treated with DNA-damaging agents, Chk1 is activated and phosphorylates Cdc10 at its carboxy-terminal domain. This modification is responsible for the repression of MBF-dependent transcription through induced release of MBF from chromatin. This inactivation of MBF is important for survival of cells challenged with DNA-damaging agents. Thus Yox1 and Cdc10 couple normal cell cycle regulation in unperturbed conditions and the DNA replication and DNA damage checkpoints into a single transcriptional complex.
