Identification of the mismatch repair genes PMS2 and MLH1 as p53 target genes by using serial analysis of binding elements
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The ability to determine the global location of transcription factor binding sites in vivo is important for a comprehensive understanding of gene regulation in human cells. We have developed a technology, called serial analysis of binding elements (SABE), involving subtractive hybridization of chromatin immunoprecipitation-enriched DNA fragments followed by the generation and analysis of concatamerized sequence tags. We applied the SABE technology to search for p53 target genes in the human genome, and have identified several previously described p53 targets in addition to numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2 . Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron. These two genes may serve as a sensor in DNA repair mechanisms and a critical determinant for the decision between cell-cycle arrest and apoptosis. These results also demonstrate the potential for use of SABE as a broadly applicable means to globally identify regulatory elements for human transcription factors in vivo .
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PMS2 and MLH1 were believed to be p53-activated targets, but meta-analysis data show this unlikely.
“The DNA repair genes PMS2 and MLH1 were also believed to be p53-activated targets,175 but meta-analysis data show this unlikely to be the case18 (Supplementary Table S2).”
From Census and evaluation of p53 target genes (2017) · cites this paper as [175]
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- Authors
- Chen, J., & Sadowski, I.
- Affiliations
- University of British Columbia (CA)
- ORCID
- Sadowski, Ivan
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-03-21
- Volume
- 102
- Issue
- 13
- Pages
- 4813-4818
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC555698
- OpenAlex
- W2032109237
- Cited by
- 111
- References
- 34
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 4 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 4
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- p53 target genes, PMS2, MLH1, DNA mismatch repair, transcription factor binding sites, p53 response elements, DNA damage response, cell cycle arrest, apoptosis, gene expression regulation, chromatin immunoprecipitation
- MeSH terms
- MutL Protein Homolog 1, Mismatch Repair Endonuclease PMS2, Adenosine Triphosphatases, Binding Sites, Carrier Proteins, DNA-Binding Proteins, Gene Expression Regulation, Humans, Luciferases, Neoplasm Proteins, Nuclear Proteins, Nucleic Acid Hybridization, Oligonucleotide Probes, Genome, Human, Tumor Suppressor Protein p53, Sequence Analysis, DNA, DNA Primers, Jurkat Cells, Reverse Transcriptase Polymerase Chain Reaction, Base Pair Mismatch, Genomics, DNA Repair Enzymes, Chromatin Immunoprecipitation, Adaptor Proteins, Signal Transducing
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