Gcn5 and SAGA Regulate Shelterin Protein Turnover and Telomere Maintenance

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2009 Aug 18

PMID 19683498

Citations 103

Authors

Boyko S Atanassov

Yvonne A Evrard

Asha S Multani

Zhijing Zhang

Laszlo Tora

Didier Devys

Sandy Chang

Sharon Y R Dent

Affiliations

Soon will be listed here.

Abstract

Histone acetyltransferases (HATs) play important roles in gene regulation and DNA repair by influencing the accessibility of chromatin to transcription factors and repair proteins. Here, we show that deletion of Gcn5 leads to telomere dysfunction in mouse and human cells. Biochemical studies reveal that depletion of Gcn5 or ubiquitin-specific protease 22 (Usp22), which is another bona fide component of the Gcn5-containing SAGA complex, increases ubiquitination and turnover of TRF1, a primary component of the telomeric shelterin complex. Inhibition of the proteasome or overexpression of USP22 opposes this effect. The USP22 deubiquitinating module requires association with SAGA complexes for activity, and we find that depletion of Gcn5 compromises this association in mammalian cells. Thus, our results indicate that Gcn5 regulates TRF1 levels through effects on Usp22 activity and SAGA integrity.

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