title: Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in γ-irradiation-induced DNA damage responses.
abstract: We show here that γ-irradiation leads to the translocation of endogenous Werner syndrome helicase (WRN) from nucleoli to nucleoplasmic DNA double strand breaks (DSBs), and WRN plays a role in damage repair. The relocation of WRN after irradiation was perturbed by promyelocytic leukemia protein (PML) knockdown and enhanced by PML IV overexpression. PML IV physically interacted with WRN after irradiation. Amino acids (a.a.) 394 to 433 of PML were necessary for this interaction and the nucleoplasmic translocation of WRN and were involved in DSB repair and cellular sensitivity to γ-irradiation. Taken together, our results provide molecular support for a model in which PML IV physically interacts with and regulates the translocation of WRN for DNA damage repair through its 394-433 a.a. domain.
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, P. R. China.
authors.forename: Jilai
authors.initials: J
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Song
authors.forename: Junjie
authors.initials: J
authors.lastname: Qian
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Baolei
authors.initials: B
authors.lastname: Tian
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Sun
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005720:Gamma Rays; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding / Q000528:radiation effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000528:radiation effects; D053484:RecQ Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase