• Interactome of vertebrate GAF/ThPOK reveals its diverse functions in gene regulation and DNA repair

    • Fulltext

       

        Click here to view fulltext PDF


      Permanent link:
      https://www.ias.ac.in/article/fulltext/jbsc/045/0038

    • Keywords

       

      Vertebrate GAF; ThPOK; DNA repair; protein-interactome; skin cutaneous melanoma

    • Abstract

       

      GAGA associated factor (GAF) is a sequence-specific DNA binding transcription factor that is evolutionarilyconserved from flies to humans. Emerging evidence shows a context-dependent function of vertebrate GAF(vGAF, a.k.a. ThPOK) in multiple processes like gene activation, repression, and enhancer-blocking. Wehypothesize that context-dependent interaction of vGAF with a diverse set of proteins forms the basis for themultifunctional nature of vGAF. To this end, we deciphered the protein–protein interactome of vGAF andshow that vGAF interacts with chromatin remodelers, RNA metabolic machinery, transcriptional activators/repressors, and components of DNA repair machinery. We further validated the biological significance of ourprotein–protein interaction data with functional studies and established a novel role of vGAF in DNA repairand cell-survival after UV-induced DNA damage. One of the major risk factors for skin cutaneous melanoma isprolonged exposure of UV and subsequent DNA damage. vGAF is highly expressed in normal skin tissue.Interestingly, our analysis of high-throughput RNA-sequencing data shows that vGAF is heavily downregulatedacross all major stages of skin cutaneous melanoma suggesting its potential as a diagnostic biomarker.Taken together, our study provides a plausible explanation for the diverse gene regulatory functions of vGAFand unravels its novel role in DNA repair.

    • Author Affiliations

       

      AVINASH SRIVASTAVA1 RAKESH K MISHRA1

      1. CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad 500 007, India
    • Dates

       
    • Supplementary Material

       
  • Journal of Biosciences | News

    • Editorial Note on Continuous Article Publication

      Posted on July 25, 2019

      Click here for Editorial Note on CAP Mode

© 2021-2022 Indian Academy of Sciences, Bengaluru.