DNA Damage and Genomic Instability Induced by Inappropriate DNA Re-Replication
Abstract
Chromosomal rearrangements and changes in copy number at various genomic loci are hallmarks of cancer cells and may be very early steps in tumorigenesis. The origins of genomic insults are poorly understood and this proposal aims to characterize one potential source of genomic instability, inappropriate DNA re-replication. In a normal eukaryotic cell cycle, the chromosomal DNA of a cell is replicated once, and only once, during S phase to ensure that each daughter cell receives exactly one complement of genomic material. By perturbing the regulation of several proteins involved in replication initiation, our laboratory has been able to conditionally induce varying amounts of re-replication in yeast cells. In this reporting period, we have shown that re-replication induces a rapid and significant decrease in cell viability and a cellular DNA damage response. Strikingly, we have observed DNA damage in the absence of a classical replication stress response. These results indicate that re-replication generates DNA damage, and raise the possibility that this could in turn lead to genomic instability.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA436928
Entities
People
- Brian M. Green
Organizations
- University of California, San Francisco