Vertebrate WRNIP1 and BLM are required for efficient maintenance of genome stability.
Bloom syndrome (BS) is rare autosomal recessive disorder associated with chromosomal instability. The gene responsible for BS, BLM, encodes a protein belonging to the RecQ helicase family. Disruptions of the SGS1 gene of Saccharomyces cerevisiae, which encodes the RecQ helicase homologue in the budding yeast, causes accelerated aging, and this phenotype is enhanced by the disruption of MGS1, the budding yeast homologue for WRNIP1. To examine the functional relationship between RecQ and WRNIP1 in vertebrate cells, we generated and characterized wrnip1/blm cells derived from the chicken B-lymphocyte line DT40. wrnip1/blm cells showed an additive elevation of sister chromatid exchange (SCE), suggesting that both genes independently contribute to the suppression of excess SCE formation. The double mutants were more sensitive to DNA damage from camptothecin (CPT), but not to damage from methyl methanesulfonate, than either single mutant. This result suggests that WRNIP1 and BLM function independently to repair DNA or induce tolerance to the lesions induced by CPT.
Hayashi
Tomoko
T
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
Seki
Masayuki
M
Inoue
Eri
E
Yoshimura
Akari
A
Kusa
Yumiko
Y
Tada
Shusuke
S
Enomoto
Takemi
T
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001816:Bloom Syndrome / Q000235:genetics; D002478:Cells, Cultured; D002645:Chickens; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D053484:RecQ Helicases; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D012854:Sister Chromatid Exchange
D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases