Discovery and Development of Inhibitors That Selectively Interfere With Cyclin-Dependent Kinase Substrate Recognition

Abstract

The Origin Recognition Complex is thought to recognize Origins of Replication and recruit replication initiation factors in mammalian cells. The loading of this complex on DNA origins is required for replication in lower organisms, and it is thought that these proteins are important for replication control in higher eukaryots. In this funding cycle we show that both ORC1 and ORC2 are important for DNA replication in the breast cancer cell line MCFl0A. Furthermore, ORC1 seems to be required for the chromatin loading for not only Pre-replicative complex components such as MCM's, but for the other Orc proteins as well. Interestingly, depletion of ORC2, but not ORC1 results in a cell cycle checkpoint that blocks the cells in Gi phase with low S-phase CDK activity. This suggests that benign breast cancer cells have a mechanism to prevent replication when ORC2 levels are low.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2003
Accession Number
ADA420174

Entities

People

  • Anindya Dutta
  • Jamie Tear

Organizations

  • Brigham and Women's Hospital

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chromosome Structures
  • Diseases And Disorders
  • Electronic Mail
  • Eukaryotes
  • Information Operations
  • Inhibition
  • Inhibitors
  • Kinases
  • Neoplasms
  • Recognition
  • Substrates

Fields of Study

  • Biology
  • Computer science

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics