Replication stress induced site-specific phosphorylation targets WRN to the ubiquitin-proteasome pathway

Fengtao Su; Souparno Bhattacharya; Salim Abdisalaam; Shibani Mukherjee; Hirohiko Yajima; Yanyong Yang; Ritu Mishra; Kalayarasan Srinivasan; Subroto Ghose; David J. Chen; Steven M. Yannone; Aroumougame Asaithamby

doi:10.18632/oncotarget.6659

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers: Gerotarget (Focus on Aging):

Replication stress induced site-specific phosphorylation targets WRN to the ubiquitin-proteasome pathway

Fengtao Su, Souparno Bhattacharya, Salim Abdisalaam, Shibani Mukherjee, Hirohiko Yajima, Yanyong Yang, Ritu Mishra, Kalayarasan Srinivasan, Subroto Ghose, David J. Chen, Steven M. Yannone and Aroumougame Asaithamby _

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2016; 7:46-65. https://doi.org/10.18632/oncotarget.6659

Metrics: PDF 2322 views | HTML 3957 views | ?

Abstract

Fengtao Su1, Souparno Bhattacharya1, Salim Abdisalaam1, Shibani Mukherjee2, Hirohiko Yajima1,4, Yanyong Yang1, Ritu Mishra1, Kalayarasan Srinivasan1, Subroto Ghose2, David J. Chen1, Steven M. Yannone3 and Aroumougame Asaithamby1

1 Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

2 Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, USA

3 Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA

4 Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan

Correspondence to:

Aroumougame Asaithamby, email:

Keywords: Werner syndrome protein, Werner syndrome, replication stress, post-translational modification,chromosome instability, Gerotarget

Received: November 06, 2015 Accepted: November 23, 2015 Published: December 18, 2015

Abstract

Faithful and complete genome replication in human cells is essential for preventing the accumulation of cancer-promoting mutations. WRN, the protein defective in Werner syndrome, plays critical roles in preventing replication stress, chromosome instability, and tumorigenesis. Herein, we report that ATR-mediated WRN phosphorylation is needed for DNA replication and repair upon replication stress. A serine residue, S1141, in WRN is phosphorylated in vivo by the ATR kinase in response to replication stress. ATR-mediated WRN S1141 phosphorylation leads to ubiquitination of WRN, facilitating the reversible interaction of WRN with perturbed replication forks and subsequent degradation of WRN. The dynamic interaction between WRN and DNA is required for the suppression of new origin firing and Rad51-dependent double-stranded DNA break repair. Significantly, ATR-mediated WRN phosphorylation is critical for the suppression of chromosome breakage during replication stress. These findings reveal a unique role for WRN as a modulator of DNA repair, replication, and recombination, and link ATR-WRN signaling to the maintenance of genome stability.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 6659

Publication Alerts

Research Papers: Gerotarget (Focus on Aging):

Replication stress induced site-specific phosphorylation targets WRN to the ubiquitin-proteasome pathway

Abstract