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

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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.

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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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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, P. R. China

    Jilai Liu, Yi Song, Junjie Qian, Bin Liu, Yan Dong, Baolei Tian & Zhixian Sun

Authors
  1. Jilai Liu
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  2. Yi Song
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  3. Junjie Qian
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  4. Bin Liu
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  5. Yan Dong
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  6. Baolei Tian
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  7. Zhixian Sun
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Corresponding authors

Correspondence to Yi Song or Zhixian Sun.

Additional information

These authors contributed equally to this work.

Published in Russian in Biokhimiya, 2011, Vol. 76, No. 5, pp. 673–679.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM10-310, February 13, 2011.

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Liu, J., Song, Y., Qian, J. et al. Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in γ-irradiation-induced DNA damage responses. Biochemistry Moscow 76, 550–554 (2011). https://doi.org/10.1134/S000629791105004X

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  • DOI: https://doi.org/10.1134/S000629791105004X

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