Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells.
Bloom syndrome (BS) is a recessive human genetic disorder characterized by short stature, immunodeficiency and an elevated risk of malignancy. The gene mutated in BS, BLM, encodes a RecQ-type DNA helicase. BS cells have mutator phenotypes such as hyper-recombination, chromosome instability and an increased frequency of sister chromatid exchange (SCE). To define the primary role of BLM, we generated BLM(-/-) mutants of the chicken B-cell line DT40. In addition to characteristics of BLM(-/-) cells reported previously by the other group, they are hypersensitive to genotoxic agents such as etoposide, bleomycin and 4-nitroquinoline-1-oxide and irradiation with the short wave length of UV (UVC) light, whereas they exhibit normal sensitivity to X-ray irradiation and hydroxyurea. UVC irradiation to BLM(-/-) cells during G(1) to early S phase caused chromosomal instability such as chromatid breaks and chromosomal quadriradials, leading to eventual cell death. These results suggest that BLM is involved in surveillance of base abnormalities in genomic DNA that may be encountered by replication forks in early S phase. Such surveillance would maintain genomic stability in vertebrate cells, resulting in the prevention of cellular tumorigenesis.
Imamura
O
O
AGENE Research Institute, 200 Kajiwara, Kamakura, Kanagawa 247-0063, Japan.
Fujita
K
K
Shimamoto
A
A
Tanabe
H
H
Takeda
S
S
Furuichi
Y
Y
Matsumoto
T
T
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D001816:Bloom Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D002455:Cell Division / Q000235:genetics*; D002461:Cell Line, Transformed / Q000528:radiation effects; D002645:Chickens; D003001:Cloning, Molecular; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D018390:Gene Targeting; D005822:Genetic Vectors; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods; D010641:Phenotype; D016133:Polymerase Chain Reaction; D053484:RecQ Helicases; D016196:S Phase / Q000235:genetics*; D012854:Sister Chromatid Exchange / Q000235:genetics*
D017931:DNA Primers; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases