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Regulation of RAD53 by the ATM -Like Kinases MEC1 and TEL1 in Yeast Cell Cycle Checkpoint Pathways
Abstract
Mutants of the Saccharomyces cerevisiae ataxia telangiectasia mutated ( ATM ) homolog MEC1/SAD3/ESR1 were identified that could live only if the RAD53/SAD1 checkpoint kinase was overproduced. MEC1 and a structurally related gene, TEL1 , have overlapping functions in response to DNA damage and replication blocks that in mutants can be provided by overproduction of RAD53 . Both MEC1 and TEL1 were found to control phosphorylation of Rad53p in response to DNA damage. These results indicate that RAD53 is a signal transducer in the DNA damage and replication checkpoint pathways and functions downstream of two members of the ATM lipid kinase family. Because several members of this pathway are conserved among eukaryotes, it is likely that a RAD53 -related kinase will function downstream of the human ATM gene product and play an important role in the mammalian response to DNA damage.
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“Mec1 controls the checkpoint by direct phosphorylation of target proteins but also via phosphorylation of downstream effector kinases, most notably the kinases Rad53 and Chk1 (11, 43, 49).”
From A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in Saccharomyces cerevisiae (2010) · cites this paper as [43]
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Metadata
- Authors
- Sanchez, Y., Desany, B. A., Jones, W. J., Liu, Q., Wang, B., & Elledge, S. J.
- Affiliations
- Verna and Mars McLean Department of Biochemistry, Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
- Howard Hughes Medical Institute (US)
- Corresponding author
- Elledge, Stephen J.
- Venue
- Science
- Published
- 1996-01-19
- Volume
- 271
- Issue
- 5247
- Pages
- 357-360
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2102433010
- Cited by
- 585
- References
- 32
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 9 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 11 · 2019: 17 · 2018: 6 · 2017: 13 · 2016: 19 · 2015: 15 · 2014: 15 · 2013: 14 · 2012: 12
- FWCI
- 13.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM-44664)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK07696, T32DK007696)
- 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
- Rad53, Mec1, Tel1, DNA damage checkpoint, S-phase checkpoint, Saccharomyces cerevisiae, signal transduction, DNA damage response, replication block
- MeSH terms
- Base Sequence, Cell Cycle, DNA Damage, DNA Replication, DNA-Binding Proteins, Fungal Proteins, Genes, Fungal, Molecular Sequence Data, Mutation, Phosphorylation, Protein Kinases, Proteins, Saccharomyces cerevisiae, Signal Transduction, Gene Expression Regulation, Fungal, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2
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