Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome. Deubiquitinates ZNF304, hence may prevent ZNF304 degradation by the proteasome, leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs). Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Belongs to the peptidase C19 family. USP28 subfamily.