Functional relation among RecQ family helicases RecQL1, RecQL5, and BLM in cell growth and sister chromatid exchange formation.
Human RECQL1 and RECQL5 belong to the RecQ family that includes Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome causative genes. Cells derived from individuals suffering from these syndromes show significant levels of genomic instability. However, neither RECQL1 nor RECQL5 has been related to a disease, and nothing is known about the functions of RecQL1 and RecQL5. We generated here RECQL1(-/-), RECQL5(-/-), RECQL1(-/-)/RECQL5(-/-), RECQL1(-/-)/BLM(-/-), and RECQL5(-/-)/BLM(-/-) cells from chicken B-lymphocyte line DT40 cells. Although BLM(-/-) DT40 cells showed a slow-growth phenotype, a higher sensitivity to methyl methanesulfonate than the wild type, and an approximately 10-fold increase in the frequency of sister chromatid exchange (SCE) compared to wild-type cells, RECQL1(-/-), RECQL5(-/-), and RECQL1(-/-)/RECQL5(-/-) cells showed no significant difference from the wild-type cells in growth, sensitivity to DNA-damaging agents, and the frequency of SCE. However, both RECQL1(-/-)/BLM(-/-) and RECQL5(-/-)/BLM(-/-) cells grew more slowly than BLM(-/-) cells because of the increase in the population of dead cells, indicating that RecQL1 and RecQL5 are somehow involved in cell viability under the BLM function-impaired condition. Surprisingly, RECQL5(-/-)/BLM(-/-) cells showed a higher frequency of SCE than BLM(-/-) cells, indicating that RecQL5 suppresses SCE under the BLM function-impaired condition.
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Wensheng
W
Wang
Masayuki
M
Seki
Yoshiyasu
Y
Narita
Takayuki
T
Nakagawa
Akari
A
Yoshimura
Makoto
M
Otsuki
Yoh-ichi
Y
Kawabe
Shusuke
S
Tada
Hideki
H
Yagi
Yutaka
Y
Ishii
Takemi
T
Enomoto
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D018929:Cell Culture Techniques; D002455:Cell Division; D002645:Chickens; D002869:Chromosome Aberrations; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry* / Q000378:metabolism*; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D053484:RecQ Helicases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012854:Sister Chromatid Exchange; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays
D016685:Mitomycin; D004247:DNA; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506731:RECQL4 protein, human; D004265:DNA Helicases; D053484:RecQ Helicases; D001973:Bromodeoxyuridine