UHRF2 promotes DNA damage response by decreasing p21 via RING finger domain
To investigate the interaction of E3 ubiquitin ligase UHRF2 with p21 and the mechanism of UHRF2 in repairing DNA damage caused by hydroxyurea (HU) in HEK293 cells.
Western blotting indicated that the overexpression of UHRF2 reduced the level of p21, particularly in HEK293 cells. Immunoprecipitation and immunofluorescence staining reveled that UHRF2 combined with p21 in the nucleus. In addition, UHRF2 degraded p21 through ubiquitination and shortened the half-life of p21. UHRF2 could repair DNA damage caused by HU treatment, which was impaired by the inhibition of p21 in HEK293 cells.
UHRF2 may negatively modulate p21 to regulate DNA damage response, suggesting a novel pathway of UHRF2 repairing DNA damage through the partial regulation of p21.
KeywordsDegradation DNA damage response P21 Ubiquitination UHRF2
This study was supported by National Natural Science Foundation of China (No. 81772178).
Supplementary Fig. 1—Structure diagrams of UHRF2 and the deletion mutants. The four main domains (UBL, PHD, SRA/YDG and RING) and a tandem Tudor (TTD) domain of UHRF2 were shown in diagrams. Four deletion mutants (ΔUBL, ΔPHD, ΔYDG and ΔRING) were created for this study.
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Conflict of interest
The authors declared no conflicts of interest.