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Related Experiment Videos

Human TopBP1 ensures genome integrity during normal S phase.

Ja-Eun Kim1, Sarah A McAvoy, David I Smith

  • 1Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Molecular and Cellular Biology
|November 30, 2005
PubMed
Summary

Human TopBP1 monitors DNA replication during S phase, preventing genomic instability. Its absence causes DNA breaks and aberrant cell division, highlighting its crucial role in maintaining genome stability.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Cell cycle checkpoints are crucial for genomic integrity.
  • Human TopBP1 (hTopBP1) is homologous to proteins involved in DNA replication and checkpoints in other species.
  • Previous studies showed hTopBP1's role in replication and DNA damage checkpoints.

Purpose of the Study:

  • To investigate the physiological function of TopBP1 during S phase.
  • To understand TopBP1's role in maintaining genomic stability in normal and stressed conditions.

Main Methods:

  • Small interfering RNA (siRNA) was used to deplete TopBP1.
  • Analysis of DNA replication, H2AX phosphorylation, ATM-Chk2 activation, and cell division.
  • Recruitment of TopBP1 to replicating chromatin was observed.

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Main Results:

  • TopBP1 is recruited to replicating chromatin during S phase.
  • TopBP1 is not essential for DNA replication itself.
  • TopBP1 deficiency leads to increased DNA double-strand breaks, H2AX phosphorylation, and ATM-Chk2 activation.
  • TopBP1-deficient cells exhibit fragile site breaks, 4N DNA content, and abnormal cell division.

Conclusions:

  • TopBP1 functions to monitor ongoing DNA replication.
  • TopBP1 is critical for maintaining genomic stability during normal S phase and after genotoxic stress.