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Significance PCNA is an essential protein in DNA replication and repair, and these functions rely on multiple posttranslational modifications, including small ubiquitin-like modifiers SUMO1 and SUMO2. SUMO2-conjugated PCNA has a distinct function in maintaining genomic stability from SUMO1-conjugated PCNA. Therefore, different SUMO E3 ligases are needed to provide the specificity to covalently attach either SUMO1 or SUMO2 to PCNA in response to different replication stress. However, even though SUMO-conjugated PCNA molecules have been observed in human cells since 2012, to date, the SUMO E3 ligases for PCNA have yet to be identified. This paper reports a SUMO E3 ligase that directly conjugates SUMO2 to PCNA with high specificity to prevent transcription induced DNA breaks in human cells.

TRIM28 functions as the SUMO E3 ligase for PCNA in prevention of transcription induced DNA breaks