Work

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

Year: 2020

Type: article

Abstract: In human cells, the DNA replication factor proliferating cell nuclear antigen (PCNA) can be conjugated to either the small ubiquitinlike modifier SUMO1 or SUMO2, but only SUMO2-conjugated PCNA is induced by transcription to facilitate resolution of transcription-replication conflict (TRC). To date, the SUMO E3 ligase that provides substrate specificity for SUMO2-PCNA conjugation in response to TRC remains unknown. Using a proteomic approach, we identified TRIM28 as the E3 ligase that catalyzes SUMO2-PCNA conjugation. In vitro, TRIM28, together with the RNA polymerase II (RNAPII)-interacting protein RECQ5, promotes SUMO2-PCNA conjugation but inhibits SUMO1-PCNA formation. This activity requires a PCNA-interacting protein (PIP) motif located within the bromodomain of TRIM28. In cells, TRIM28 interaction with PCNA on human chromatin is dependent on both transcription and RECQ5, and SUMO2-PCNA level correlates with TRIM28 expression. As a consequence, TRIM28 depletion led to RNAPII accumulation at TRC sites, and expression of a TRIM28 PIP mutant failed to suppress TRC-induced DNA breaks.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2004122117

Authors: Min Li, Xiaohua Xu, Chou-Wei Chang, Yilun Liu

Institutions: City Of Hope National Medical Center, City of Hope, Beckman Research Institute

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Cancer Institute, National Institute of General Medical Sciences

Awards: The function of Topoisomerase I SUMOylation in transcription and chemoresistance, G772794905, RECQ5-dependent SUMO2 conjugation of PCNA in the resolution of transcription-replication conflicts