HSCARG, a novel regulator of H2A ubiquitination by downregulating PRC1 ubiquitin E3 ligase activity, is essential for cell proliferation.

Abstract:

:Histone H2A ubiquitination plays critical roles in transcriptional repression and deoxyribonucleic acid (DNA) damage response. More attention has been focused on ubiquitin E3 ligases of H2A, however, less is known about the negative regulators of H2A ubiquitination. Here we identified HSCARG as a new negative regulatory protein for H2A ubiquitination and found a possible link between regulator of H2A ubiquitination and cell cycle. Mechanistically, HSCARG interacts with polycomb repressive complex 1 (PRC1) and deubiquitinase USP7 and inhibits PRC1 ubiquitination in a USP7-dependent manner. As ubiquitination of PRC1 is critical for its E3 ligase activity toward H2A, HSCARG and USP7 are further shown to decrease the level of H2A ubiquitination. Moreover, we demonstrated that HSCARG is involved in DNA damage response through affecting the level of H2A ubiquitination and localization of RAP80 at lesion points. Knockout of HSCARG results in persistent activation of checkpoint signaling and leads to cell cycle arrest. This study unravels a novel mechanism for the regulation of H2A ubiquitination and elucidates how regulators of H2A ubiquitination affect cell cycle.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Hu B,Li S,Zhang X,Zheng X

doi

10.1093/nar/gku230

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

5582-93

issue

9

eissn

0305-1048

issn

1362-4962

pii

gku230

journal_volume

42

pub_type

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