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The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor

Title: The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor
Authors: Ivanova, Tsvetomira; Alves-Rodrigues, Isabel; Gomez-Escoda, Blanca; Dutta, Chaitali; DeCaprio, James A.; Rhind, Nicholas; Hidalgo, Elena; Ayte, Jose
Contributors: Department of Biochemistry and Molecular Pharmacology
Source: Molecular biology of the cell ; 24 ; 21 ; 3350-7
Publication Year: 2022
Collection: University of Massachusetts, Medical School: eScholarship@UMMS
Subject Terms: Blotting; Western; CDC2 Protein Kinase; Cell Cycle Proteins; DNA Damage; DNA Replication; DNA; Fungal; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation; Homeodomain Proteins; Mutation; Phosphorylation; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; Schizosaccharomyces; Schizosaccharomyces pombe Proteins; Transcription Factors; Cell Biology; Cellular and Molecular Physiology; Molecular Biology; Molecular Genetics
Description: 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: Link to Article in PubMed; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814153/; http://hdl.handle.net/20.500.14038/30544; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1822&context=faculty_pubs&unstamped=1; https://escholarship.umassmed.edu/faculty_pubs/820; 7880396; faculty_pubs/820
DOI: 10.1091/mbc.E13-05-0257
Availability: https://doi.org/10.1091/mbc.E13-05-0257; https://hdl.handle.net/20.500.14038/30544; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1822&context=faculty_pubs&unstamped=1; https://escholarship.umassmed.edu/faculty_pubs/820
Rights: Copyright © 2013 Ivanova et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License ( http://creativecommons.org/licenses/by-nc-sa/3.0 ). ; http://creativecommons.org/licenses/by-nc-sa/3.0/
Accession Number: edsbas.B4AF7F59
Database: BASE