Exogenous expression of exonuclease domain-deleted WRN interferes with the repair of radiation-induced DNA damages.
Werner syndrome (WS) is an autosomal recessive disease characterized by multiple progeroid features. The gene responsible for WS, WRN, is a member of the human RecQ helicase family. WRN is unique among this family, associated with an exonuclease activity. In the present study, we established the human 293-derived cell lines, which expressed exogenously truncated WRN protein, lacking the N-terminal exonuclease domain but having normal helicase activity, and found that they were slightly, but nonetheless significantly, radiosensitive than control cell lines, into which the empty vector had been introduced. The truncated WRN-expressing cells also exhibited increased numbers of micronuclei, chromosome aberrations, and the foci of phosphorylated histone H2AX with X-rays. These results suggested a function of WRN exonuclease activity that is separable from helicase activity and is essential for the repair of radiation-induced DNA damages.
Kashino
Genro
G
Division of Radiation Biology, Department of Radiology and Radiation Biology, Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, Japan.
Kodama
Seiji
S
Suzuki
Keiji
K
Matsumoto
Takehisa
T
Watanabe
Masami
M
D002460:Cell Line; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology*; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D005090:Exodeoxyribonucleases; D005092:Exonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000502:physiology* / Q000528:radiation effects*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D017434:Protein Structure, Tertiary; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology; D053484:RecQ Helicases; D000071657:Werner Syndrome Helicase
D004247:DNA; D005090:Exodeoxyribonucleases; D005092:Exonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase