A checkpoint regulates the rate of progression through S phase in S. cerevisiae in Response to DNA damage
Open accessAbstract
We demonstrate that in S. cerevisiae the rate of ongoing S phase is slowed when the DNA is subjected to alkylation. Slowing of replication is dependent on the MEC1 and RAD53 genes, indicating that lesions alone do not slow replication in vivo and that the slowing is an active process. While it has been shown that a MEC1- and RAD53-dependent checkpoint responds to blocked replication or DNA damage by inhibiting the onset of mitosis, we demonstrate that this checkpoint must also have an additional target within S phase that controls replication rate. MEC1 is a homolog of the human ATM gene, which is mutated in ataxia telangiectasia (AT) patients. Like mec1 yeast, AT cells are characterized by damage-resistant DNA synthesis, highlighting the congruence of the yeast and mammalian systems.
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In Saccharomyces cerevisiae, Mec1 protein kinase is the most important component of the damage checkpoint and is the yeast homologue of human ATR.
“In Saccharomyces cerevisiae, the most important of these is the Mec1 protein kinase, the yeast homologue of human ATR (26, 39, 45).”
From A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in <i>Saccharomyces cerevisiae</i> (2010) · cites this paper as [39]
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References 44 · Cited by 588
- Authors
- Paulovich, A. G., & Hartwell, L. H.
- Affiliations
- University of Washington (US)
- ORCID
- Paulovich, Amanda G
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1995-09
- Volume
- 82
- Issue
- 5
- Pages
- 841-847
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2090601888
- Cited by
- 588
- References
- 44
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 15 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 10 · 2016: 11 · 2015: 9 · 2014: 15 · 2013: 19 · 2012: 17
- FWCI
- 15.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- DNA damage checkpoint, S phase progression, DNA replication rate, alkylation, Mec1, Rad53, ataxia telangiectasia, Saccharomyces cerevisiae, DNA damage response
- MeSH terms
- Cell Division, DNA Damage, DNA Replication, Fungal Proteins, Genes, Fungal, Saccharomyces cerevisiae, S Phase
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