Identification of Proteins Required for Repair of Double-Strand Chromosome Breaks, a Predisposing Factor in Breast Cancer
Abstract
Defects in repair of double strand chromosome breaks (DSBs) are emerging as important factors both in familial and sporadic breast tumors. Just as a bacterial model for single-base mismatch repair lead to rapid identification of human homologues with roles in carcinogeneis, development of a bacterial model for DNA DSB repair will provide important insights into the role this system plays in breast tumor development. Our work toward development of a model for bacterial DSB repair by replication coupled to recombination has progressed significantly during the course of this grant contract period. We determined that the Escherichia coli PriA protein is absolutely required for coupling DNA replication with recombination both in vivo and in vitro. PriA specifically recognized a replication origin created by recombination and showed a preference for forked DNA structures in gel shift assays. PriA's 3' to 5' helicase activity unwound the DNA at a fork and promoted loading of the replicative helicase DnaB, a central step in assembly of the replisome. These data indicate that PriA is an initiator protein that responds to DNA damage and assembles the components necessary for repair by replication, maintaining the integrity of the chromosome and preventing potentially catastrophic loss of information and mutation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1999
- Accession Number
- ADA389908
Entities
People
- Jessica M Jones
Organizations
- Georgetown University