RNF20-RNF40: A ubiquitin-driven link between gene expression and the DNA damage response

Ubiquitin and the DNA damage response

The rapid accumulation of signaling and repair factors in the vicinity of DNA lesions is an integral part of the cellular DNA damage response (DDR) to DNA double-strand breaks (DSBs).1,2 This is initiated by posttranslational modifications of core histones, to which various effector proteins bind. The priming modification is ATM-mediated phosphorylation of histone H2AX at Ser-139 (γ-H2AX), a ma...

CRL Ubiquitin Ligases and DNA Damage Response

Cullin/RING ubiquitin ligases (CRL) comprise the largest subfamily of ubiquitin ligases. CRLs are involved in cell cycle regulation, DNA replication, DNA damage response (DDR), development, immune response, transcriptional regulation, circadian rhythm, viral infection, and protein quality control. One of the main functions of CRLs is to regulate the DDR, a fundamental signaling cascade that mai...

Editorial: Ubiquitin and Ubiquitin-Relative SUMO in DNA Damage Response

Arsenite Binds to the RING Finger Domains of RNF20-RNF40 Histone E3 Ubiquitin Ligase and Inhibits DNA Double-Strand Break Repair

Arsenic is a widespread environmental contaminant. However, the exact molecular mechanisms underlying the carcinogenic effects of arsenic remain incompletely understood. Core histones can be ubiquitinated by RING finger E3 ubiquitin ligases, among which the RNF20-RNF40 heterodimer catalyzes the ubiquitination of histone H2B at lysine 120. This ubiquitination event is important for the formation...

Deficiency in mammalian histone H2B ubiquitin ligase Bre1 (Rnf20/Rnf40) leads to replication stress and chromosomal instability.

Mammalian Bre1 complexes (BRE1A/B (RNF20/40) in humans and Bre1a/b (Rnf20/40) in mice) function similarly to their yeast homolog Bre1 as ubiquitin ligases in monoubiquitination of histone H2B. This ubiquitination facilitates methylation of histone H3 at K4 and K79, and accounts for the roles of Bre1 and its homologs in transcriptional regulation. Recent studies by others suggested that Bre1 act...