Abstract
Insertion/deletion (IDL) mismatches in DNA are lesions consisting of extra bases on one strand. Here, the binding of p53 and its 14 kDa C-terminal domain to DNAs containing one or three 3-cytosine IDL mismatches was examined. Electron microscopy showed that both p53 forms bound predominantly as tetramers at the lesions while single-stranded binding proteins did not bind. Gel retardation assays showed that p53 formed highly stable complexes when the DNA contained the IDL mismatches, but only unstable complexes when the DNA lacked lesions (but did contain free ends). The highly stable complexes had a half-life of > 2 hr, suggesting that upon encountering lesions, p53 may recruit other proteins to the site, providing a signal for DNA damage.
Keywords
BiologyDNAMolecular biologyDNA damageDNA-binding proteinCytosineCell biologyBiophysicsBiochemistryGene
MeSH Terms
Base CompositionBase SequenceBinding SitesDNADNA DamageElectrophoresisPolyacrylamide GelHumansMicroscopyElectronMolecular Sequence DataMutagenesisInsertionalOligodeoxyribonucleotidesPeptide FragmentsRecombinant ProteinsSequence DeletionTemplatesGeneticTumor Suppressor Protein p53
Affiliated Institutions
Related Publications
Activation of p53 sequence-specific DNA bindingby short single strands of DNA requires the p53 C-terminus
Upon cellular DNA damage, the p53 tumor suppressor protein transmits a signal to genes that control the cell cycle and apoptosis. One function of p53 that is important for its r...
Allosteric activation of latent p53 tetramers
The DNA-binding activity of p53 is essential to its function as a tumour suppressor. Point mutations that abolish this activity have been found to occur frequently in the p53 ge...
Presence of a Potent Transcription Activating Sequence in the p53 Protein
The p53 gene is frequently mutated in a wide variety of human cancers. However, the role of the wild-type p53 gene in growth control is not known. Hybrid proteins that contain t...
Domains of the Glucocorticoid Receptor Involved in Specific and Nonspecific Deoxyribonucleic Acid Binding, Hormone Activation, and Transcriptional Enhancement
We have analyzed the domain structure of the mouse glucocorticoid receptor by expression of in vitro mutated receptor in COS-7 cells. The receptor consists of a core domain rich...
Induction of apoptosis in HeLa cells by trans-activation-deficient p53.
The p53 tumor suppressor protein is a transcriptional activator, which can mediate apoptotic cell death in a variety of cell types. To determine whether sequence-specific trans-...
Publication Info
- Year
- 1995
- Type
- article
- Volume
- 81
- Issue
- 7
- Pages
- 1013-1020
- Citations
- 402
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
402
OpenAlex
7
Influential
282
CrossRef
Cite This
Suman Lee,
Brian Elenbaas,
Arnold J. Levine
et al.
(1995).
p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches.
Cell
, 81
(7)
, 1013-1020.
https://doi.org/10.1016/s0092-8674(05)80006-6
Identifiers
- DOI
- 10.1016/s0092-8674(05)80006-6
- PMID
- 7600570