Cited by 113DNA Repair MechanismsFungal and yeast genetics researchBacterial Genetics and Biotechnology

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Requirement of the Mre11 Complex and Exonuclease 1 for Activation of the Mec1 Signaling Pathway

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Nakada, Daisuke, Hirano, Yukinori, Sugimoto, Katsunori·2004·Molecular and Cellular Biology

DOI 10.1128/mcb.24.22.10016-10025.2004PMC PMC525484

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Abstract

The large protein kinases, ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR), orchestrate DNA damage checkpoint pathways. In budding yeast, ATM and ATR homologs are encoded by TEL1 and MEC1, respectively. The Mre11 complex consists of two highly related proteins, Mre11 and Rad50, and a third protein, Xrs2 in budding yeast or Nbs1 in mammals. The Mre11 complex controls the ATM/Tel1 signaling pathway in response to double-strand break (DSB) induction. We show here that the Mre11 complex functions together with exonuclease 1 (Exo1) in activation of the Mec1 signaling pathway after DNA damage and replication block. Mec1 controls the checkpoint responses following UV irradiation as well as DSB induction. Correspondingly, the Mre11 complex and Exo1 play an overlapping role in activation of DSB- and UV-induced checkpoints. The Mre11 complex and Exo1 collaborate in producing long single-stranded DNA (ssDNA) tails at DSB ends and promote Mec1 association with the DSBs. The Ddc1-Mec3-Rad17 complex associates with sites of DNA damage and modulates the Mec1 signaling pathway. However, Ddc1 association with DSBs does not require the function of the Mre11 complex and Exo1. Mec1 controls checkpoint responses to stalled DNA replication as well. Accordingly, the Mre11 complex and Exo1 contribute to activation of the replication checkpoint pathway. Our results provide a model in which the Mre11 complex and Exo1 cooperate in generating long ssDNA tracts and thereby facilitate Mec1 association with sites of DNA damage or replication block.

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Authors: Nakada, D., Hirano, Y., & Sugimoto, K.
Affiliations: Rutgers New Jersey Medical School (US)
Corresponding author: Sugimoto, Katsunori
ORCID: Nakada, Daisuke
Hirano, Yukinori
Sugimoto, Katsunori
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2004-11
Volume: 24
Issue: 22
Pages: 10016-10025
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.24.22.10016-10025.2004
PMC: PMC525484
OpenAlex: W2110555186
Cited by: 113
References: 68
Citations by year: 2023: 2 · 2022: 1 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 9 · 2012: 4
FWCI: 5.09
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: Mre11 complex, EXO1, Mec1, DNA damage checkpoint, DNA double-strand breaks, single-stranded DNA, DNA end resection, S-phase checkpoint, UV-induced DNA damage, Tel1, Saccharomyces cerevisiae
MeSH terms: DNA Damage, DNA Replication, DNA-Binding Proteins, DNA, Fungal, Endodeoxyribonucleases, Exodeoxyribonucleases, Fungal Proteins, Genes, Fungal, Models, Biological, Mutation, Phleomycins, Phosphoproteins, Phosphorylation, Saccharomyces cerevisiae, Transcription Factors, Signal Transduction, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Replication Protein A, Checkpoint Kinase 2

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Requirement of the Mre11 Complex and Exonuclease 1 for Activation of the Mec1 Signaling Pathway

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