TY - JOUR
T1 - UBAP2/UBAP2L regulate UV-induced ubiquitylation of RNA polymerase II and are the human orthologues of yeast Def1
AU - Herlihy, Anna E.
AU - Boeing, Stefan
AU - Weems, Juston C.
AU - Walker, Jane
AU - Dirac-Svejstrup, A. Barbara
AU - Lehner, Michelle Harreman
AU - Conaway, Ronald C.
AU - Conaway, Joan W.
AU - Svejstrup, Jesper Q.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - Def1
KW - RNA polymerase II ubiquitylation
KW - Transcription-coupled nucleotide excision repair
KW - UBAP2
KW - UBAP2L
KW - Ubiquitin
UR - http://www.scopus.com/inward/record.url?scp=85131052968&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85131052968&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2022.103343
DO - 10.1016/j.dnarep.2022.103343
M3 - Article
C2 - 35633597
AN - SCOPUS:85131052968
SN - 1568-7864
VL - 115
JO - DNA repair
JF - DNA repair
M1 - 103343
ER -