A SUMO Atlas shoulders the DNA damage response (477.3)

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The maintenance of genomic integrity requires multiple types of protein modification that are readily reversible and therefore capable of dynamic signaling and regulation. Our lab has been studying how protein modification by SUMO (small ubiquitin‐like modifier) contributes to the maintenance of the genome. Studies from our lab and others have shown that mutating sumoylation and desumoylation enzymes results in multiple defects in DNA repair and chromosomal segregation. For example, mutating the sumoylation E2 and the Mms21 E3 enzymes in yeast leads to the accumulation of toxic recombination intermediates when cells replicate over damaged templates. Some of these defects can be partly explained by the lack of modification of known DNA metabolism substrates, such as PCNA, Rad52, and TDG, sumoylation of which can modulate their DNA repair functions. However, majority of the phenotypes seen in mutants of the sumoylation enzymes cannot be explained by the lack of sumoylation of the previously known SUMO substrates. This indicates the existence of additional targets that contribute to the roles of sumoylation in genome maintenance. We have undertaken a biochemical approach to identify new sumoylation substrates and have examined how sumoylation contributes to the cellular response to DNA damage, both at a global level and at the individual substrate level. Our results indicate the existence of an extensive DNA damage‐induced sumoylation system that makes multiple contributions to genome stability and operates largely independent of the canonical DNA damage checkpoint kinase. Our progress to understand this new system and its effects will be reported and discussed.