International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 117 - FUNCTION OF RECQ DNA HELICASES BLM AND RECQL5 IN THE SUPPRESSION OF MITOTIC CROSSOVERS AND MAINTENANCE OF GENOMIC STABILITY

Hu Y, Barnes E, Luo G

Case Western Reserve University, Cleveland, United States

Homologous recombination (HR) is important for both mitotic and meiotic cells. HR can lead to either crossover or gene conversion without crossover upon completion. In somatic cells, crossovers can cause genome rearrangements,and must be suppressed by specific mechanisms. Previous studies have shown that BLM, a RecQ DNA helicase, has important roles in such suppression. Mutations in the BLM gene in humans cause Bloom syndrome (BS), a disorder with unusually high tumor susceptibility. The elevated frequency of mitotic crossovers in BS cells leads to a significantly increased frequency of sister chromatid exchange (SCE), as well as triradial and quadriradial structures. Interestingly, while BLM is the only known gene to suppress mitotic crossovers in mammals, recent studies in yeast suggest additional mechanisms exist. Therefore, it is important to investigate whether other pathways are also present in mammals. In addition to our previously reported mouse model for BS, we generated knockout mice for another RecQ family member, Recql5. Analysis in Recql5-/- cells revealed that the frequency of spontaneous SCE increased to a comparable level of that observed in Blm-/- cells. Triradial and quadriradial structures were also seen in these cells. Frequency of SCE was further elevated in the double knockout cells of Blm and Recql5. These observations provide the first genetic evidence that Recql5 suppresses mitotic crossovers in a parallel but non-redundant manner with Blm. Studies with other cell types and knockout mice are in progress to investigate the function of Recql5 and its genetic interaction with Blm in HR regulation and maintenance of genomic stability.

[an error occurred while processing this directive]