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Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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...
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...

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Visualization of DNA Repair Proteins Interaction by Immunofluorescence
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Published on: June 26, 2020

AsSIRTing the DNA damage response.

Myriam Gorospe1, Rafael de Cabo

  • 1Laboratory of Cellular and Molecular Biology, National Institute on Aging - Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. myriam-gorospe@nih.gov

Trends in Cell Biology
|January 25, 2008
PubMed
Summary
This summary is machine-generated.

The HuR protein stabilizes sirtuin 1 (SIRT1) mRNA, boosting SIRT1 protein levels. This enhances DNA repair by enabling ATM protein to phosphorylate NBS1, maintaining genomic integrity after genotoxic stress.

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Area of Science:

  • Cellular biology
  • Molecular genetics
  • DNA repair mechanisms

Background:

  • Mammalian cells possess signaling networks and proteins to manage damaged macromolecules.
  • Genotoxic stress triggers cellular responses to maintain homeostasis.

Purpose of the Study:

  • To review an emergent pathway for maintaining homeostasis after genotoxic stress.
  • To elucidate the regulatory pathway involving HuR, SIRT1, and NBS1 in genomic integrity maintenance.

Main Methods:

  • Review of existing literature on RNA-binding proteins, sirtuins, and DNA damage response pathways.
  • Analysis of the post-transcriptional and post-translational regulation of key proteins.

Main Results:

  • The RNA-binding protein HuR associates with sirtuin 1 (SIRT1) mRNA, maintaining elevated SIRT1 protein levels.
  • SIRT1 deacetylates the Nijmegen breakage syndrome (NBS1) protein, facilitating its phosphorylation by ATM (ataxia telangiectasia mutated) protein.
  • NBS1, a component of the MRN complex, is critical for sensing DNA damage and initiating a genotoxic response.

Conclusions:

  • The HuR-->SIRT1-->NBS1 pathway represents a critical mechanism for maintaining genomic integrity.
  • Post-transcriptional and post-translational modifications play vital roles in cellular response to genotoxic stress.