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Elongin and the Elongin A ubiquitin ligase complex in transcription and the response to DNA damage
Author(s) -
Weems Juston Cory,
Conaway Joan,
Conaway Ron
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.457.28
Subject(s) - rna polymerase ii , ubiquitin ligase , ubiquitin , dna damage , biology , microbiology and biotechnology , transcription (linguistics) , dna ligase , dna repair , protein subunit , transcription factor , dna , genetics , gene expression , gene , promoter , linguistics , philosophy
Lesions induced by a variety of DNA damaging agents can block RNA polymerase II (Pol II) elongation. Mechanisms that reactivate or remove Pol II that has become stalled or arrested at such lesions are critical for resumption of gene expression after DNA damage repair and, in addition, may contribute to efficiency of the DNA repair process by enhancing access of the damage repair machinery to the lesion. Following exposure of cells to UV irradiation or other DNA damaging agents, Pol II is ubiquitinated in a transcription‐coupled reaction and degraded by the proteasome, and it has been proposed that ubiquitination and degradation of Pol II stalled at DNA lesions may contribute to transcription‐coupled DNA repair and/or to reactivation of transcription after repair of the damaged DNA. Elongin is a multisubunit complex that was first identified and purified as an activity that stimulates the rate at which Pol II elongates nascent transcripts in vitro. Elongin is composed of 3 subunits, Elongin A (ELOA), the ubiquitin‐like protein Elongin B (ELOB), and Elongin C (ELOC), which is similar to the SCF ubiquitin ligase subunit Skp1. Elongin A performs dual functions in cells as a component of RNA polymerase II (Pol II) transcription elongation factor Elongin and as the substrate recognition subunit of a Cullin‐RING (CRL) E3 ubiquitin ligase that has been shown to target Pol II stalled at sites of DNA damage. Here we investigate the mechanism(s) governing conversion of the Elongin complex from its elongation factor to its ubiquitin ligase form. We find that assembly of the Elongin A ubiquitin ligase is a tightly regulated process. In unstressed cells, the majority of Elongin A is found as part of Pol II elongation factor Elongin. Assembly of Elongin A into the ubiquitin ligase is strongly induced by genotoxic stress, by transcriptional stresses that lead to accumulation of stalled Pol II, and by other stimuli, including endoplasmic reticulum and nutrient stress and retinoic acid signaling, that activate Elongin A‐dependent transcription. We will describe ongoing studies to define signal transduction pathways that lead to assembly and activation of the Elongin A‐ubiquitin ligase as well as experiments addressing the possibility that the Elongin A ubiquitin ligase plays a more direct role in Elongin A‐dependent transcription activation than previously anticipated. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .