How Alterations in the Cdt1 Expression Leads to Gene Amplification in Breast Cancer

Abstract

We examined the effects of Cdt1 for gene amplification by using inducible system. We Obtained and validated reagents for inducible Cdt1-expression-system. Furthermore, we identified appropriated dose of MTX for testing gene amplification Cdt2 is a key molecule for inhibiting Cdt1 activity. The depletion of Cdt2 induces DNA rereplication in several cell lines. During experiment, we Identified a reduction of PCNA monoubiquitination in Cdt2 depleted MCF7 cells. Exogenous Cdt2 rescued the effect of si-Cdt2. Mutant of Cdt2 indicated that binding Cdt2 to Cul4/DDB1 was required for PCNA monoubiquitination. Furthermore, we identified that CRL4Cdt2 complex promotes PCNA-dependent translesion DNA synthesis.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2009
Accession Number
ADA514046

Entities

People

  • Kenta Terai

Organizations

  • University of Virginia

Tags

DTIC Thesaurus Topics

  • Amplification
  • Antigens
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Carrier Proteins
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Colon Cancer
  • Damage
  • Degradation
  • Department Of Defense
  • Molecules
  • Neoplasms
  • Proteins

Readers

  • Molecular Biology and Genetics