The DOI matches its Crossref record; 101 of the 101 references it cites were found in a registry or an index.
Tip60: Connecting chromatin to DNA damage signaling
Open accessAbstract
Cells are constantly exposed to genotoxic events that can damage DNA. To counter this, cells have evolved a series of highly conserved DNA repair pathways to maintain genomic integrity. The ATM protein kinase is a master regulator of the DNA double-strand break (DSB) repair pathway. DSBs activate ATM's kinase activity, promoting the phosphorylation of proteins involved in both checkpoint activation and DNA repair. Recent work has revealed that two DNA damage response proteins, the Tip60 acetyltransferase and the mre11- rad50-nbs1 (MRN) complex, co-operate in the activation of ATM in response to DSBs. MRN functions to target ATM and the Tip60 acetyltransferase to DSBs. Tip60's chromodomain then interacts with histone H3 trimethylated on lysine 9, activating Tip60's acetyltransferase activity and stimulating the subsequent acetylation and activation of ATM's kinase activity. These results underscore the importance of chromatin structure in regulating DNA damage signaling and emphasize how histone modifications co-ordinate DNA repair. In addition, human tumors frequently exhibit altered patterns of histone methylation. This rewriting of the histone methylation code in tumor cells may impact the efficiency of DSB repair, increasing genomic instability and contributing to the initiation and progression of cancer.
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Citations
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Metadata
- Authors
- Sun, Y., Jiang, X., & Price, B. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Price, Brendan D.
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2010-03
- Volume
- 9
- Issue
- 5
- Pages
- 930-936
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC2901859
- OpenAlex
- W2072607093
- Cited by
- 230
- References
- 85
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 11 · 2023: 9 · 2022: 14 · 2021: 13 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 5 · 2016: 28 · 2015: 19 · 2014: 18 · 2013: 18 · 2012: 18
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- National Cancer Institute (T32 CA09078, R01CA064585, R01CA093602, CA09078, CA64585, T32CA009078, CA93602)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- Tip60, ATM kinase, DNA double-strand break repair, DNA damage response, MRN complex, histone H3 lysine 9 trimethylation, chromodomain, chromatin structure, histone modifications, genomic instability, cancer
- MeSH terms
- Lysine Acetyltransferase 5, MRE11 Homologue Protein, Chromatin, DNA Repair, DNA-Binding Proteins, Histones, Humans, Signal Transduction, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, Histone Acetyltransferases, DNA Breaks, Double-Stranded, Ataxia Telangiectasia Mutated Proteins
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