Fig. 4.

Regulatory functions of ubiquitination in DNA repair. E3 ligases usually participate in DNA damage response and DNA double-strand repair through degradation-dependent function. Specifically, during DNA damage response, H2AX can be degraded through SMURF2 and HUWEI-mediated ubiquitination, and USP3, USP22, and USP17L2 can eliminate the ubiquitin chains. During homologous recombination, BRCA1 can be degraded by HERC2 and stabilized by USP9X. In the NHEJ process, XRCC4 is ubiquitinated by FBXW7 for degradation. DNA-PK is degraded through RNF144A-mediated ubiquitination. During mismatch repair, HDAC6 ubiquitinates MSH2 for further protein degradation, which can be reversed by USP10. In the regulation of cell cycle check points, RNF4 promotes ubiquitination of MDC1, and ataxin-3 and USP7 deubiquitinate MDC1, therefore controlling the stability of MDC1. MDM2 facilitates the ubiquitinoylation of p53 for degradation, while USP4, USP24, USP7, and USP28 remove the ubiquitin chain. USP7 stabilizes CDC25A. PIRH2 and SIAH2 promote ubiquitin-dependent degradation of CHK2, and USP39 eliminates the ubiquitin chains. HDAC6 and HUWEI induce CHK1 ubiquitination, while USP3 and USP7 deubiquitinate the CHK1