STUbLs in chromatin and genome stability

Abstract

Chromatin structure and function is based on the dynamic interactions between nucleosomes and chromatin‐associated proteins. In addition to the other post‐translational modifications considered in this review issue of Biopolymers, ubiquitin and SUMO proteins also have prominent roles in chromatin function. A specialized form of modification that involves both, referred to as SUMO‐targeted ubiquitin ligation, or STUbL [Perry, Tainer, and Boddy, Trends Biochem Sci, 2008, 33, 201–208], has significant effects on nuclear functions, ranging from gene regulation to genomic stability. Intersections between SUMO and ubiquitin in protein modification have been the subject of a recent comprehensive review [Praefcke, Hofmann, and Dohmen, Trends Biochem Sci, 2012, 37, 23–31]. Our goal here is to focus on features of enzymes with STUbL activity that have been best studied, particularly in relation to their nuclear functions in humans, flies, and yeasts. Because there are clear associations of disease and development upon loss of STUbL activities in metazoans, learning more about their function, regulation, and substrates will remain an important goal for the future. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 146–154, 2013.

SUMO-targeted ubiquitin ligase (STUbL) Slx5 regulates proteolysis of centromeric histone H3 variant Cse4 and prevents its mislocalization to euchromatin

“…, 2009 ; Hickey et al. , 2012 ; Garza and Pillus, 2013 ; Sriramachandran and Dohmen, 2014 ). Slx5, but not Slx8, has been shown to associate with centromeres, and slx5 ∆ and slx8 ∆ mutants show defects in chromosome segregation ( van de Pasch et al.…”

Pds5 Prevents the PolySUMO-Dependent Separation of Sister Chromatids

“…Target proteins can be monoSUMOylated (at one or multiple sites) and/or sport polymeric SUMO chains, which form primarily on SUMO lysines 11, 15, and 19 in a Siz1-or Siz2-dependent manner [28,29,40]. While SUMO chains are not essential for cell viability in budding yeast, they impinge on multiple aspects of chromatin regulation [38], and their uncontrolled accumulation has been proposed to underlie the overall cell fitness defect of ulp2D mutants [28,29,[40][41][42][43].…”

Targeting of SUMO substrates to a Cdc48–Ufd1–Npl4 segregase and STUbL pathway in fission yeast

“…Given the diversity of SUMO conjugates in the cell, other proteins are likely to be targeted by STUbLs under normal or perturbed conditions. Indeed, STUbLs have been detected at centromeres, nuclear pores, replication forks and at sites of DNA damage 17 18 .…”