A Role for H2B Ubiquitylation in DNA Replication

Abstract

SUMMARY The monoubiquitylation of histone H2B plays an important role in gene expression by contributing to the regulation of transcription elongation and mRNA processing and export. We explored additional cellular functions of this histone modification by investigating its localization to intergenic regions. H2B ubiquitylation is present in chromatin around origins of DNA replication in budding yeast, and as DNA is replicated its levels are maintained on daughter strands by the Bre1 ubiquitin ligase. In the absence of H2B ubiquitylation, the pre-replication complex is formed and activated, but replication fork progression is slowed down and the replisome becomes unstable in the presence of hydroxyurea. H2B ubiquitylation promotes the assembly or stability of nucleosomes on newly replicated DNA, and this function is postulated to contribute to fork progression and replisome stability.

Functional Analysis of Bre1p, an E3 Ligase for Histone H2B Ubiquitylation, in Regulation of RNA Polymerase II Association with Active Genes and Transcription in Vivo

“…Furthermore, similar to the ⌬rad6 strain, the ⌬bre1 strain shows sensitivity to genotoxic agents such as MMS and HU (Fig. 1I), consistent with previous studies (16,25,47).…”

(Ubi)quitin’ the h2bit: recent insights into the roles of H2B ubiquitylation in DNA replication and transcription

“…9 The authors also confirmed an earlier report that H3 occupancy at replication origins during S phase under HU is reduced in cells lacking H2B. 9,16 Such a finding suggests defective assembly and/or stability of nucleosomes in the absence of H2Bub. Such H2Bub-mediated nucleosome assembly behind the replication fork may slow replication by (i) impeding the movement of the replication fork during the subsequent round of replication, or (ii) transmitting a signal to the fork during the current round of replication.…”

“…14,15 Yeast cells lacking H2Bub are hypersensitive to HU, and H2Bub was thus hypothesized to relieve replication stress. 16 While testing this hypothesis, Lin et al made the unexpected finding that replication fork progression is faster in H2Bub-deficient mutants than in wild-type cells under HU stress, when observed at the genome-wide level. 9 Importantly, the increase in fork progression appears to be independent of DNA damageinduced ribonucleotide production, suggesting that H2Bub may play a direct role in regulating fork progression.…”

Stabilization and targeting of INO80 to replication forks by BAP1 during normal DNA synthesis

“…A recent study reported that H2B monoubiquitination at Lys-120 (H2Bub) has an important role in fork progression and replisome stability in yeast 38 . Interestingly, we observed that H2Bub was also associated with replication forks (Fig.…”