Journal Article

p53 protein at the hub of cellular DNA damage response pathways through sequence-specific and non-sequence-specific DNA binding

Yuangang Liu and Molly Kulesz-Martin

in Carcinogenesis

Volume 22, issue 6, pages 851-860
Published in print June 2001 | ISSN: 0143-3334
Published online June 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.6.851
p53 protein at the hub of cellular DNA damage response pathways through sequence-specific and non-sequence-specific DNA binding

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Our environment contains physical, chemical and pathological agents that challenge the integrity of our DNA. In addition to DNA repair, higher multicellular organisms have evolved multiple pathways of response to damage including programmed cell death—apoptosis. The p53 protein appears to sense multiple types of DNA damage and coordinate with multiple options for cellular response. The p53 protein activities depend upon its DNA binding. Specific p53 protein post-translational modifications are required for efficient sequence-specific binding and transcriptional activities. Non-sequence-specific DNA binding may involve a wide spectrum of p53 proteins and predominate as DNA damage is more severe or p53 protein is more highly induced. p53 protein is not strictly required for DNA damage sensing and repair. Rather, p53 protein may govern an apoptosis checkpoint through competition with DNA repair proteins for non-sequence-specific binding to exposed single-stranded regions in the DNA duplex. This model provides a framework for testing mechanisms of p53-mediated apoptosis dependent upon the p53 protein modification state, the level of p53 protein accumulation, the level of DNA damage and the capacity of the damaged cell to repair.

Keywords: BER, base excision repair; CAK, cyclin-activated kinase; dsDNA, double-stranded DNA; NER, nucleotide excision repair; RPA, replication protein A; ssDNA, single-stranded DNA; sds-DNA, single-stranded/double-stranded DNA transition.

Journal Article.  9857 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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