ATR/Mec1: coordinating fork stability and repair
Abstract
During S phase, eukaryotic cells unwind and duplicate a tremendous amount of DNA, generating structures that are very sensitive to both endogenous and exogenous insults. The collision of DNA polymerases with damaged DNA or other obstructions to fork progression generates replication stress, which can evolve into fork collapse if the replisome components are not stabilized. To ensure genome integrity, stalled replication forks are recognized by a checkpoint, whose central player is the human kinase ATR or Mec1 in S. cerevisiae. This review will discuss recent findings revealing roles of the ATR/Mec1 kinase: both in stabilizing the replisome directly and in activating the checkpoint response to regulate origin firing, DNA repair, fork restart, and cell cycle progression.
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Mec1 phosphorylates serine and threonine residues that are immediately adjacent to a glutamine (SQ/TQ motifs).
“Mec1 phosphorylates serine and threonine residues that are immediately adjacent to a glutamine (SQ/TQ motifs) (14).”
From A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in <i>Saccharomyces cerevisiae</i> (2010) · cites this paper as [14]
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References 52 · Cited by 157
- Authors
- Friedel, A. M., Pike, B. L., & Gasser, S. M.
- Affiliations
- Friedrich Miescher Institute (CH)
- Corresponding author
- Gasser, Susan M
- Venue
- Current Opinion in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 21
- Issue
- 2
- Pages
- 237-244
- ISSN
- 0955-0674 (ISSN-L)
- OpenAlex
- W2046469401
- Cited by
- 157
- References
- 52
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 9 · 2019: 3 · 2018: 3 · 2017: 12 · 2016: 9 · 2015: 13 · 2014: 10 · 2013: 16 · 2012: 12
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Bureau of Land Management
- 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 › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- ATR kinase, Mec1 kinase, replication fork stability, replication stress, DNA damage checkpoint, replisome, DNA repair, origin firing, fork restart, cell cycle progression, S phase, genome stability
- MeSH terms
- Checkpoint Kinase 1, Animals, Cell Cycle, DNA Damage, DNA Repair, DNA Replication, Enzyme Activation, Humans, Protein Kinases, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, Genomic Instability, Intracellular Signaling Peptides and Proteins, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2
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