Association of the bloom syndrome protein with topoisomerase III alpha in somatic and meiotic cells

Bloom syndrome (BS) is characterized by genomic instability and cancer susc eptibility caused by defects in BLM, a DNA helicase of the RecQ-family (J, German and N, A. Ellis, The Genetic Basis of Human Canter, pp, 301.-316, 19 98), RecQ helicases and topoisomerase III proteins interact physically and functionally in yeast (S, Gangloff et al,, Mel. Cell. Biol,, 14: 8391-8398, 1994) and in Escherichia coli can function together to enable passage of d ouble-stranded DNA (F, G, Harmon et al., Mel. Cell, 3: 611-620, 1999), We d emonstrate in somatic and meiotic human cells an association between BLM an d topoisomerase III alpha, These proteins colocalize in promyelocytic leuke mia protein nuclear bodies, and this localization is disrupted in BS cells. Thus, mechanisms by which RecQ helicases and topoisomerase III proteins co operate to maintain genomic stability in model organisms likely apply to hu mans.