The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
ATR Kinase Activation Mediated by MutSα and MutLα in Response to Cytotoxic O6-Methylguanine Adducts
Open accessAbstract
S(N)1-type alkylating agents that produce cytotoxic O(6)-methyl-G (O(6)-meG) DNA adducts induce cell cycle arrest and apoptosis in a manner requiring the DNA mismatch repair (MMR) proteins MutSalpha and MutLalpha. Here, we show that checkpoint signaling in response to DNA methylation occurs during S phase and requires DNA replication that gives rise to O(6)-meG/T mispairs. DNA binding studies reveal that MutSalpha specifically recognizes O(6)-meG/T mispairs, but not O(6)-meG/C. In an in vitro assay, ATR-ATRIP, but not RPA, is preferentially recruited to O(6)-meG/T mismatches in a MutSalpha- and MutLalpha-dependent manner. Furthermore, ATR kinase is activated to phosphorylate Chk1 in the presence of O(6)-meG/T mispairs and MMR proteins. These results suggest that MMR proteins can act as direct sensors of methylation damage and help recruit ATR-ATRIP to sites of cytotoxic O(6)-meG adducts to initiate ATR checkpoint signaling.
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In the citing paper
“This suggests DNA repair proteins may regulate the DDR pathway directly or indirectly [99, 196, 197].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [197]
In the citing paper
“DNA repair proteins (such as DNA nucleases) may process DNA damage into structures for DDR protein recruitment or recruit DDR proteins to damaged sites via direct protein–protein interactions.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [197]
In the citing paper
“SN1-type DNA alkylating agents induce DNA adducts, such as O6-meG (O6-methylguanine), and activate the ATR-Chk1 pathway.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [197]
In the citing paper
“indicating MutSα plays an upstream role for ATR checkpoint signaling [197]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [197]
In the citing paper
“MutSα also recruits ATR-ATRIP to O6-meG:T”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [197]
In the citing paper
“suggesting that MMR proteins can act as direct sensors of mismatches with methylation damage.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [197]
In the citing paper
“MutSα specifically recognizes O6-meG:T mismatch, but not O6-meG:C”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [197]
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Citations
Cites
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Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
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Proteome survey reveals modularity of the yeast cell machinery
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ATR and ATRIP: Partners in Checkpoint Signaling
Cortez, D., Guntuku, S., Qin, J., & Elledge, S. J. (2001) · Science · doi:10.1126/science.1065521 · Cited by 985
TopBP1 Activates the ATR-ATRIP Complex
Kumagai, A., Lee, J., Yoo, H. Y., & Dunphy, W. G. (2006) · Cell · doi:10.1016/j.cell.2005.12.041 · Cited by 787
DNA Mismatch Repair: Molecular Mechanisms and Biological Function
Schofield, M. J., & Hsieh, P. (2003) · Annual Review of Microbiology · doi:10.1146/annurev.micro.57.030502.090847 · Cited by 498
Self-citationPI 3-kinase related kinases: ?big? players in stress-induced signaling pathways
Abraham, R. T. (2004) · DNA repair · doi:10.1016/j.dnarep.2004.04.002 · Cited by 461
An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair.
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ATR: an essential regulator of genome integrity
Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798
DNA repair pathways as targets for cancer therapy
Helleday, T., Petermann, E., Lundin, C., Hodgson, B., & Sharma, R. A. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2342 · Cited by 1,666
DNA damage-induced cell death by apoptosis
Roos, W. P., & Kaina, B. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.07.007 · Cited by 1,500
Mechanisms and functions of DNA mismatch repair
Li, G. (2007) · Cell Research · doi:10.1038/cr.2007.115 · Cited by 1,479
Balancing repair and tolerance of DNA damage caused by alkylating agents
Fu, D., Calvo, J. A., & Samson, L. D. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3185 · Cited by 977
Metadata
- Authors
- Yoshioka, K.-I., Yoshioka, Y., & Hsieh, P.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Hsieh, Peggy
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 22
- Issue
- 4
- Pages
- 501-510
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC2423943
- OpenAlex
- W2163529853
- Cited by
- 288
- References
- 49
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 12 · 2023: 4 · 2022: 14 · 2021: 15 · 2020: 8 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 13 · 2015: 15 · 2014: 9 · 2013: 15 · 2012: 13
- FWCI
- 11.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Massachusetts General Hospital
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK052029)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- MutSα, MutLα, DNA mismatch repair, DNA replication checkpoint, S phase, Chk1 phosphorylation, DNA damage recognition
- MeSH terms
- Animals, Base Sequence, Carrier Proteins, Cell Line, DNA, DNA Damage, DNA Repair, DNA-Binding Proteins, Enzyme Activation, Exodeoxyribonucleases, Guanine, HeLa Cells, Humans, Nuclear Proteins, Phosphoproteins, Signal Transduction, S Phase, Protein Serine-Threonine Kinases, DNA Adducts, Cell Cycle Proteins, Base Pair Mismatch, Adaptor Proteins, Signal Transducing, Mice, MutS DNA Mismatch-Binding Protein, Ataxia Telangiectasia Mutated Proteins
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