Homologous Recombination—Fixing Severe DNA Damage in Humans
To repair one of the most severe forms of DNA damage, a double-strand break, eukaryotic organisms, from yeast to humans, initiate a process called homologous recombination: Enzymes organize into a presynaptic complex that attaches to the broken DNA at the point of damage; then the presynaptic complex locates a homologous sequence—an undamaged DNA sequence elsewhere in the cell’s genome that corresponds to the damaged one and can serve as a template for restoring lost genetic information. Researchers have characterized some of the enzymes and other mechanisms that control homologous recombination during meiosis in the yeast Saccharomyces cerevisiae. Many of these may be shared with humans, but we still have much to learn about homologous recombination in humans, during both meiosis and mitosis.
J. Brooks Crickard, Molecular Biology and Genetics, is investigating the enzymes and other mechanisms that contribute to meiotic and mitotic homologous recombination in humans. Among other goals, this project seeks to understand how enzymes arrange themselves into presynaptic complexes that direct homologous recombination differently during mitosis versus meiosis, and how these complexes promote the correct alignment of damaged DNA with a homologous sequence to successfully repair a double-strand break.
Failure to repair DNA double-strand breaks can lead to a loss of genomic integrity and the development of aneuploidy-related illnesses. Findings from this research will be used to better understand processes by which organisms repair double-strand breaks. The long-term goal of this research is to inform development of novel tools and strategies that better treat diseases resulting from a loss in genomic integrity.
NIH Award Number: 1R35GM142457-01