Biochemistry (Moscow)

, Volume 76, Issue 5, pp 550–554

Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in γ-irradiation-induced DNA damage responses

Article

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 over-expression. 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.

Key words

PML WRN γ-irradiation DNA damage DNA repair 

Abbreviations

ATM

ataxia-telangiectasia mutated protein

DAPI

4′,6-diamidino-2-phenylindol

DSB

double-strand break

GFP

green fluorescent protein

γ-H2AX

phosphorylated histone H2AX

HEL

human embryo lung fibroblasts

IRIF

ionizing radiation induced foci

PML

promyelocytic leukemia protein

PML NBs

promyelocytic leukemia nuclear bodies

WRN

Werner syndrome helicase

WS

Werner’s syndrome

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Supplementary material

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Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyBeijing Institute of Radiation MedicineBeijingP. R. China

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