Role of homologous recombination in the replication stress response

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PROJECT SUMMARY/ABSTRACT FROM PARENT AWARD Precise replication of DNA is required to maintain genome stability. Replication forks face many obstacles from Endogenous and exogenous sources that result in fork stalling or breakage threatening integrity. The double strand break repair pathway, homologous recombination, has critical roles at stalled replication forks independent of double strand breaks. The importance of this pathway is highlighted by patients with inherited chromosomal instability orders and cancer predisposition syndromes. Although an intense area of study, how recombination proteins function at replication forks are poorly understood. A comprehensive understanding of the replication response is critical for the understanding the molecular mechanisms of human disease and to lead to development of novel therapeutics for patients harboring mutations in replication response genes. The long-term goal of the PI to elucidate the roles of recombination proteins in the replication stress response. In support of this goal, the PI and laboratory have established a powerful-separation-of-function allele of the central recombination enzyme, RAD51 and uncovered a novel role for a recombination accessory protein. The successful completion of this work will lead to a better of understanding of the role recombination proteins play at stalled replication forks and how protect the integrity of the genome.