Association of the Bloom syndrome protein with topoisomerase IIIalpha in somatic and meiotic cells.
Bloom syndrome (BS) is characterized by genomic instability and cancer susceptibility caused by defects in BLM, a DNA helicase of the RecQ-family (J. German and N. A. Ellis, The Genetic Basis of Human Cancer, pp. 301-316, 1998). RecQ helicases and topoisomerase III proteins interact physically and functionally in yeast (S. Gangloff et al., Mol. Cell. Biol., 14: 8391-8398, 1994) and in Escherichia coli can function together to enable passage of double-stranded DNA (F. G. Harmon et al., Mol. Cell, 3: 611-620, 1999). We demonstrate in somatic and meiotic human cells an association between BLM and topoisomerase IIIalpha. These proteins colocalize in promyelocytic leukemia protein nuclear bodies, and this localization is disrupted in BS cells. Thus, mechanisms by which RecQ helicases and topoisomerase III proteins cooperate to maintain genomic stability in model organisms likely apply to humans.
Johnson
F B
FB
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Lombard
D B
DB
Neff
N F
NF
Mastrangelo
M A
MA
Dewolf
W
W
Ellis
N A
NA
Marciniak
R A
RA
Yin
Y
Y
Jaenisch
R
R
Guarente
L
L
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008540:Meiosis; D053484:RecQ Helicases; D014407:Tumor Cells, Cultured
D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I