SUMO-mediated regulation of DNA damage repair and responses

• Sumoylation of many DNA metabolism proteins is tightly controlled by DNA engagement.
• SUMO can influence a process through an ensemble effect or via major substrates.
• SUMO causes diverse effects, such as bi-directional changes in biomolecule binding.
• Crosstalk between SUMO and other modifiers occurs at multiple levels during DDR.

Sumoylation has important roles during DNA damage repair and responses. Recent broad-scope and substrate-based studies have shed light on the regulation and significance of sumoylation during these processes. An emerging paradigm is that sumoylation of many DNA metabolism proteins is controlled by DNA engagement. Such ‘on-site modification’ can explain low substrate modification levels and has important implications in sumoylation mechanisms and effects. New studies also suggest that sumoylation can regulate a process through an ensemble effect or via major substrates. Additionally, we describe new trends in the functional effects of sumoylation, such as bi-directional changes in biomolecule binding and multilevel coordination with other modifications. These emerging themes and models will stimulate our thinking and research in sumoylation and genome maintenance.