Functions of FUS/TLS from DNA repair to stress response: implications for ALS

ASN Neuro. 2014 Jun 1;6(4):1759091414544472. doi: 10.1177/1759091414544472.


Fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is a multifunctional DNA-/RNA-binding protein that is involved in a variety of cellular functions including transcription, protein translation, RNA splicing, and transport. FUS was initially identified as a fusion oncoprotein, and thus, the early literature focused on the role of FUS in cancer. With the recent discoveries revealing the role of FUS in neurodegenerative diseases, namely amyotrophic lateral sclerosis and frontotemporal lobar degeneration, there has been a renewed interest in elucidating the normal functions of FUS. It is not clear which, if any, endogenous functions of FUS are involved in disease pathogenesis. Here, we review what is currently known regarding the normal functions of FUS with an emphasis on DNA damage repair, RNA processing, and cellular stress response. Further, we discuss how ALS-causing mutations can potentially alter the role of FUS in these pathways, thereby contributing to disease pathogenesis.

Keywords: DNA damage repair; FUS/TLS; RNA processing; amyotrophic lateral sclerosis; stress granules; stress response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • DNA Repair / physiology*
  • Humans
  • RNA Processing, Post-Transcriptional
  • RNA-Binding Protein FUS / physiology*
  • Stress, Physiological / physiology*


  • RNA-Binding Protein FUS