Development of a Novel Genetic Assay to Study DNA Double Strand Breaks

Ohio State University, Columbus OH

Investigators

Linked publications & trials

Abstract

7. Project Summary/Abstract A DNA double strand break (DSB) which constitutes severing of a chromosome into two parts is one of the most lethal types of DNA damage because it can lead to loss of genetic information, or other forms of chromosomal rearrangements. DSBs can occur spontaneously mainly during DNA replication or be caused by external DNA damaging agents. One mechanism of DSB repair is via error-free homologous recombination (HR), a process in which missing genetic information resulting from the break is copied from another similar undamaged chromosomal region. Although HR has been studied extensively, a complete understanding of the mechanisms that govern this process has remained elusive. In recent years, multiple recombination pathways have been identified that may produce gene conversions, deletions, translocations or duplications. Analyzing the genetic requirements for all these recombination outcomes could be a daunting task. Most of the many pathways of repair have been studied independently and to our knowledge a way of simultaneously studding the contributions of all the repair pathways has not been possible. Here we propose the development of a novel assay that can simultaneously study the contribution of most recombination pathways through a simple genetic screen. We then intend to use this assay to assess the function of two chromatin remodeling genes in homologous recombination. We believe that this assay will be of tremendous interest in the field of double strand break repair and will greatly enhance our understanding of DNA damage repair. !