Abstract

Unscheduled or excessive homologous recombination (HR) can lead to gross chromosomal rearrangements characteristic of cancer cells, but the mechanisms that restrain HR remained poorly understood. We previously reported that rtel-1 mutant worms and RTEL1 depleted human cells exhibit hyper-recombination and sensitivity to DNA damaging agents. Biochemical studies revealed that RTEL1 promotes the disassembly of D loop recombination intermediates in vitro, which led us to propose that RTEL1 acts to counteract toxic recombination. More recently, we have shown that RTEL -1 is required for crossover interference and homeostasis and promotes non-crossover repair during C. elegans meiosis. Our recent efforts have focused on understanding the molecular basis of RTEL1 dysfunction in vertebrate cells; loss of Rtel1 results in reduced proliferative capacity, increased chromatid breaks, sensitivity to replication blocking lesions and telomere abnormalities. I will present our recent insights into the function of RTEL1 in controlling HR at telomeres and the activities that drive telomere dysfunction in its absence.