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DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Abnormal Proliferation02:23

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Negative Regulator Molecules01:23

Negative Regulator Molecules

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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
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Related Experiment Video

Updated: Mar 23, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Two p53 tetramers bind one consensus DNA response element.

Sinéad Kearns1, Rudi Lurz2, Elena V Orlova3

  • 1Institute for Structural and Molecular Biology, School of Biological Sciences, Birkbeck College, London WC1E 7HX, UK Wolfson Institute for Biomedical Research, Division of Medicine, University College London, London WC1E 6BT, UK.

Nucleic Acids Research
|April 2, 2016
PubMed
Summary
This summary is machine-generated.

The tumor suppressor p53 protein, a transcription factor, binds DNA response elements (RE) to regulate cellular stress responses. New research shows two p53 tetramers can bind one DNA RE simultaneously, challenging previous models.

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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

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Last Updated: Mar 23, 2026

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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

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Area of Science:

  • Molecular Biology
  • Genetics
  • Structural Biology

Background:

  • The p53 tumor suppressor is a critical transcription factor regulating cell cycle and genetic integrity.
  • p53 activation by genotoxic stress initiates DNA repair, cell cycle arrest, apoptosis, or senescence via binding to specific DNA response elements (RE).
  • The canonical p53 DNA RE comprises two decameric palindromic half-sites, with prior models suggesting one p53 tetramer binds one RE.

Purpose of the Study:

  • To investigate the binding mechanism of human and murine p53 tetramers to p53 DNA REs.
  • To elucidate the structural basis of p53-DNA interactions using biochemical and electron microscopy methods.
  • To challenge and refine existing models of p53 transcriptional regulation.

Main Methods:

  • Biochemical assays to analyze p53 DNA-binding.
  • 3D cryo-electron microscopy (cryo-EM) to determine structural interactions.
  • Analysis of human and murine p53 tetramers binding to various p53 DNA REs.

Main Results:

  • Demonstrated that two p53 tetramers can bind sequence-specifically to a single DNA RE concurrently.
  • Structural analysis via EM revealed a novel binding mode where DNA is positioned between two p53 tetramers.
  • Observed binding of full-length p53 tetramers to only one half-site of RE in previous cryo-EM studies.

Conclusions:

  • The study reveals a previously unrecognized mode of p53-DNA interaction, with two tetramers binding a single RE.
  • This finding necessitates a revision of current understanding of p53 transcriptional regulation.
  • The results have significant implications for understanding p53's role in cellular responses to stress and its function as a tumor suppressor.