Fidelity of DNA Replication in Normal and Malignant Human Brest Cells.

Abstract

In order to begin to determine the degree to which the accumulation of mutations in breast cancer cells is due to a change in the fidelity of the cellular DNA replication machinery, we have initiated experiments that utilize a multiprotein DNA replication complex (MRC) isolated from breast cancer cells and normal breast cells. The isolated MRC is finally competent to replicate template DNA in vitro and has been demonstrated by our lab to accurately depict the DNA synthetic process as it occurs in vivo. We have used the MRC from breast cancer cells and normal breast cells to replicate a target gene in an in vitro DNA replication assay. By utilizing the target gene in a bacterial mutant selection assay we have begun to determine the frequency with which mutational sequence errors occur as a result of the in vitro DNA replication mediated by the breast cancer cell MRC and the normal breast cell MRC. To date, our results suggest that the fidelity of DNA replication mediated by the breast cancer cell MRC is lower than the fidelity of the normal breast cell MRC. Nucleotide sequencing will be used to identify specific types of mutations occurring in the replicated target gene, as well as mutational hot spots in the replicated target gene.

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Document Details

Document Type
Technical Report
Publication Date
Aug 31, 1995
Accession Number
ADA300348

Entities

People

  • Jennifer Weeks

Organizations

  • University of Maryland School of Medicine

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Dna Sequence Analysis
  • Frequency
  • Hot Spots
  • Mutations
  • Neoplasms
  • Nucleotides
  • Reliability
  • Sequences
  • Template Patterns

Fields of Study

  • Biology

Readers

  • Computational Modeling and Simulation
  • Molecular Biology and Genetics
  • Nanoscale Plasmonic Nanotechnology