A Predisposing Factor In Breast Cancer: Identification Of Proteins Required For Repair Of Double-Strand Chromosome Breaks

Life Sciences & Biotechnology Update, August, 2001

This (Georgetown University) report addresses defects in the repair of double-strand chromosomal breaks (DSB), which are critical factors in familial and sporadic breast tumors. In model bacterial systems, such lesions can be ascribed to defects in homologous recombination proteins, which can support chromosomal replication by promoting restart of DNA synthesis when replication forks become arrested. The project focuses on developing a bacterial model for DSB repair, by characterizing the enzymatic apparatus needed to initiate DNA replication on recombination intermediates.

Escherichia coli PriA protein is found to play a critical function in the transition from recombination to DNA replication. PriA specifically binds to forked DNA structures created by recombination or replication fork arrest, and promotes the assembly of protein components needed to load the major replicative helicase DnaB onto the template, a critical step in initiation. DnaB requires single-stranded DNA to bind, and this could be created by the helicase action of PriA, an activity that is suppressed by single-stranded binding protein if a duplex opening is already available. These data indicate that PriA can function in the repair of damaged DNA templates by promoting assembly of replication proteins on a wide variety of forked templates, preventing catastrophic loss or alteration of genetic information.

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