2. Academic Validation
  3. UBAP2/UBAP2L regulate UV-induced ubiquitylation of RNA polymerase II and are the human orthologues of yeast Def1

UBAP2/UBAP2L regulate UV-induced ubiquitylation of RNA polymerase II and are the human orthologues of yeast Def1

  • DNA Repair (Amst). 2022 Jul;115:103343. doi: 10.1016/j.dnarep.2022.103343.
Anna E Herlihy 1,  Stefan Boeing 1,  Juston C Weems 2,  Jane Walker 1,  A Barbara Dirac-Svejstrup 3,  Michelle Harreman Lehner 1,  Ronald C Conaway 2,  Joan W Conaway 2,  Jesper Q Svejstrup 4
Affiliations

Affiliations

  • 1 Mechanisms of Transcription Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • 2 Department of Biochemistry & Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
  • 3 Mechanisms of Transcription Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3B, Copenhagen N 2200, Denmark.
  • 4 Mechanisms of Transcription Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3B, Copenhagen N 2200, Denmark. Electronic address: jsvejstrup@sund.ku.dk.
PMID: 35633597 DOI: 10.1016/j.dnarep.2022.103343
Abstract

During transcription, RNA polymerase II (RNAPII) faces numerous obstacles, including DNA damage, which can lead to stalling or arrest. One mechanism to contend with this situation is ubiquitylation and degradation of the largest RNAPII subunit, RPB1 - the 'last resort' pathway. This conserved, multi-step pathway was first identified in yeast, and the functional human orthologues of all but one protein, RNAPII Degradation Factor 1 (Def1), have been discovered. Here we show that following UV-irradiation, human Ubiquitin-associated protein 2 (UBAP2) or its paralogue UBAP2-like (UBAP2L) are involved in the ubiquitylation and degradation of RNAPII through the recruitment of Elongin-Cul5 ubiquitin Ligase. Together, our data indicate that UBAP2 and UBAP2L are the human orthologues of yeast Def1, and so identify the key missing proteins in the human last resort pathway.

Keywords

Def1; RNA polymerase II ubiquitylation; Transcription-coupled nucleotide excision repair; UBAP2; UBAP2L; Ubiquitin.

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