Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer.

Jian Cao,Qin Yan

doi:10.3389/fonc.2012.00026

Abstract

Histone post-transcriptional modifications play essential roles in regulation of all DNA related processes. Among them, histone ubiquitination has been discovered for more than three decades. However, its functions are still less well understood than other histone modifications such as methylation and acetylation. In this review, we will summarize our current understanding of histone ubiquitination and deubiquitination. In particular, we will focus on how they are regulated by histone ubiquitin ligases and deubiquitinating enzymes. We will then discuss the roles of histone ubiquitination in transcription and DNA damage response and the crosstalk between histone ubiquitination and other histone modifications. Finally, we will review the important roles of histone ubiquitination in stem cell biology and cancer.

Highlights

In the eukaryotic nucleus, genomic DNA is packaged into chromatin by forming nucleosomes
Depletion of E2, E3 for H2B monoubiquitination or mutation of Lys-123 in H2B inhibits methylation of Dam1 (Latham et al, 2011). These results suggest that H2Bub plays important roles outside of chromatin and is required for chromosome segregation
Ectopic expression of H2A fused to ubiquitin, which is a mimic of natural monoubiquitinated H2A, rescues Breast cancer type 1 susceptibility gene (BRCA1) phenotypes (Zhu et al, 2011). These findings indicate that BRCA1 maintains heterochromatin structure via monoubiquitination of H2A

Summary

INTRODUCTION

Genomic DNA is packaged into chromatin by forming nucleosomes. The histone tails protrude from the nucleosome, and are subjected to a wide array of covalent modifications include methylation, acetylation, ubiquitination, phosphorylation, sumoylation, and ADP ribosylation (Strahl and Allis, 2000) These post-transcriptional modifications work together to regulate the chromatin structure, which affects biological processes including gene expression, DNA repair, and chromosome condensation. Two other RING domain containing proteins in the PRC1 (Polycomb Repressive Complex 1) complex, RING1A, and BMI1, strongly stimulate the E3 ubiquitin ligase activity of RING1B (Cao et al, 2005; Buchwald et al, 2006).

E3 E3 E2 E3 E2 E3 E2 E2 DUB DUB DUB DUB DUB DUB DUB DUB DUB DUB DUB

CONCLUSION