Bloom's syndrome gene suppresses premature ageing caused by Sgs1 deficiency in yeast.
BACKGROUND
Bloom's syndrome (BS) is an autosomal recessive disorder causing short stature, immunodeficiency, and an increased risk of cancer. Increased rates of sister chromatid exchange and chromosomal aberration have been observed in cells having defects in the BLM gene. Among five kinds of human RecQ helicases cloned, the mutations in WRN and RecQL4 have been known as the causes of premature ageing. Little is, however, known about the function of BLM helicase in ageing.


RESULTS
We show that human BLM, but not WRN can prevent the premature ageing and the increased homologous recombination at the rDNA loci caused by sgs1 mutation. Unexpectedly, the levels of ERCs (extrachromosomal rDNA circles), the products of homologous recombination, formed in 7-generation cells of the wild-type or the sgs1:BLM strain were comparable with those of the sgs1 or the sgs1:WRN age-matched-old cells.


CONCLUSIONS
These results imply that BLM helicase may have an important role in human ageing. In addition, these data suggest that the accumulated ERCs per se may be not the cause of premature ageing in yeast, inconsistent with the model proposed by Sinclair & Guarente. We discuss a new model, which explains how Sgs1 or BLM helicase suppresses premature ageing in yeast.
Heo
S J
SJ
Department of Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639, Japan.
Tatebayashi
K
K
Ohsugi
I
I
Shimamoto
A
A
Furuichi
Y
Y
Ikeda
H
H
D019588:Aging, Premature / Q000201:enzymology / Q000235:genetics*; D001816:Bloom Syndrome / Q000235:genetics* / Q000378:metabolism*; D004265:DNA Helicases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism; D004275:DNA, Ribosomal / Q000378:metabolism; D005090:Exodeoxyribonucleases; D005656:Fungal Proteins / Q000235:genetics; D005800:Genes, Fungal; D005819:Genetic Markers; D006801:Humans; D009154:Mutation / Q000235:genetics / Q000502:physiology; D053484:RecQ Helicases; D011995:Recombination, Genetic / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic / Q000502:physiology*; D014898:Werner Syndrome; D000071657:Werner Syndrome Helicase
D004271:DNA, Fungal; D004275:DNA, Ribosomal; D005656:Fungal Proteins; D005819:Genetic Markers; D029701:Saccharomyces cerevisiae Proteins; D005090:Exodeoxyribonucleases; C090472:SGS1 protein, S cerevisiae; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase