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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...
Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
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...
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...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...

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Visualization of DNA Repair Proteins Interaction by Immunofluorescence
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INTS3 controls the hSSB1-mediated DNA damage response.

Jeffrey R Skaar1, Derek J Richard, Anita Saraf

  • 1Howard Hughes Medical Institute, New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.

The Journal of Cell Biology
|September 30, 2009
PubMed
Summary
This summary is machine-generated.

Human single-stranded binding protein 1 (hSSB1) interacts with the Integrator complex and a novel protein (MISE) to activate ATM signaling and RAD51 recruitment. This complex controls hSSB1 transcription, revealing a new DNA damage response network.

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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • Human single-stranded binding protein 1 (hSSB1) is implicated in DNA damage response pathways.
  • The ataxia telangiectasia mutated (ATM) signaling pathway is crucial for genomic stability.
  • Integrator complex subunits and uncharacterized proteins are involved in cellular processes.

Purpose of the Study:

  • To investigate the function of hSSB1 within the ATM signaling pathway.
  • To identify proteins interacting with hSSB1, particularly in its phosphorylated states.
  • To elucidate the role of novel protein complexes in the DNA damage response.

Main Methods:

  • Tandem affinity purification of hSSB1 mutants (unphosphorylated and ATM-phosphorylated).
  • Co-purification analysis to identify interacting protein partners.
  • Assessment of the functional impact of the identified complex on DNA damage response pathways.

Main Results:

  • hSSB1 mutants co-purified with Integrator complex subunits and a novel protein, INTS3-MISE.
  • The INTS3-MISE-hSSB1 complex is essential for ATM activation and RAD51 recruitment to DNA damage sites.
  • INTS3 regulates hSSB1 transcription, establishing a feedback loop within the DNA damage response network.

Conclusions:

  • A novel complex involving hSSB1, INTS3, and MISE plays a critical role in the DNA damage response.
  • This complex mediates ATM activation and RAD51 recruitment through transcriptional control of hSSB1.
  • The findings reveal a new regulatory network governing hSSB1 function and cellular response to genotoxic stress.