AUTHOR=Keiten-Schmitz Jan , Schunck Kathrin , Müller Stefan 

TITLE=SUMO Chains Rule on Chromatin Occupancy

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 7 - 2019

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2019.00343

DOI=10.3389/fcell.2019.00343

ISSN=2296-634X

ABSTRACT=The dynamic and reversible post-translational modification of proteins and protein complexes with the ubiquitin-related SUMO modifier regulates a wide variety of nuclear functions, such as transcription, replication and DNA repair.  SUMO can be attached as a monomer to its targets, but can also form polymeric SUMO chains. While monoSUMOylation is generally involved in the assembly of protein complexes, polySUMOylation may have very different consequences. The evolutionary conserved paradigmatic signaling process initiated by polySUMOylation is the SUMO-targeted Ubiquitin ligase (StUbL) pathway, where SUMO chains prime ubiquitylation by the mammalian  E3 ubiquitin ligases RNF4 or RNF111, or the yeast Slx5/8 heterodimer.  The mammalian SUMO chain-specific isopeptidases SENP6 or SENP7, or yeast Ulp2, counterbalance chain formation thereby limiting StUbL activity. Many facets of SUMO chain signaling are still incompletely understood, mainly because only a limited number of polySUMOylated substrates have been identified. Here we summarize recent work that revealed a highly interconnected network of candidate polySUMO modified proteins functioning in DNA damage response and chromatin organization. Based on these datasets and published work on distinct polySUMO-regulated processes we discuss overarching concepts in SUMO chain function. We propose a evolutionary conserved role of polySUMOylation in orchestrating chromatin dynamics and genome stability networks by balancing chromatin-residency of protein complexes. This concept will be exemplified in processes, such as centromere/kinetochore organization, sister chromatid cohesion, DNA repair and replication.