Characterisation of a novel role for the cancer-associated protein Translin in the regulation of genome stability

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Documents

  • Hussam Althagafi

    Research areas

  • PhD, School of Natural Sciences, translin and trax

Abstract

Translin and Trax are a pair of highly conserved proteins that are functionally linked with each other. They are nucleic acid binding proteins associated with in chromosome translocations in cancers. They have subsequently been demonstrated to function in a broad spectrum of biological process, including tRNA processing, mRNA regulation in neuronal cells, spermatogenesis function and in microRNA degradation in oncogenesis, the latter leading to the suggestion that they might be a drug target for a number of cancers. Given this, and the proposal that Translin is associated with the DNA damage response, set out to address whether Translin and/or Trax have a functional role in preserving genome stability. In this study, the biological role of Translin and Trax was explored using the facile experimental model system, Schizosaccharomyces pombe. A previous study had shown that both Tsn1 (Translin) and Tfx1 (Trax) did not exhibit any significant function role in S. pombe. Recently, a Translin-Trax hetero-octamer complex (C3PO) has been found to be essential in the regulation of RNA interference (RNAi). Additionally, the RNAi component Dicer (Dcr1) has been demonstrated to function in an RNAi-independent role to prevent genome instability. In order to ask whether Tsn1 and/or Tfx1 have redundant role with Dcr1, tsn1∆, tfx1∆ and dcr1∆ single and double mutants were generated and assessed for genome stability phenotypes. We find that Tsn1, but not Tfx1, plays a redundant role in controlling genome stability in the absence of Dcr1. We propose that in the absence of Dcr1, Tsn1 acts by suppressing the transcription-DNA replication-associated recombination. Given that Dcr1 has been proposed to regulate and maintain genome stability, we extend this investigation to assess if Tsn1 and/or Tfx1 have primary roles associated with the RNases H activity. This study indicates that Tsn1 functions in one of two pathway RNase H pathways. Taken together, the data represented here demonstrate a new role for Tsn1 in maintain genome stability in a pathway could be associated with RNA:DNA hybrids control so, more invistagations are required to prove that. These data offer the basis for understanding how Translin might influence oncogenic chromosomes translocations, addressing a long-standing question in chromosome biology.

Details

Original languageEnglish
Awarding Institution
  • Bangor University
Supervisors/Advisors
Award date14 Jul 2020