Table 2.
OGT and OGA substrates in DDR
| Biological processes | Protein name | Molecular details | References |
|---|---|---|---|
| Replication | MCM | Mcm3,6,7 are O-GlcNAcylated | (64) |
| Replication | Histone 4 (H4) | H4 is O-GlcNAcylated at Ser47. H4S47 O-GlcNAcylation enhances DBF4-dependent protein kinase (DDK) recruitment on chromatin, directs origin activation through facilitating MCM phosphorylation | (65) |
| Replication | TOP2A | O-GlcNAcylation at Ser1469 enhances TOP2A chromatin DNA binding and catalytic activity, leading to resistance to Adm in breast cancer cells and xenograft models | (66) |
| Replication | Flap endonuclease 1 (FEN1) | FEN1 is O-GlcNAcylated at Ser352, which disrupts its interaction with proliferating cell nuclear antigen (PCNA) at the replication foci, and leads to altered cell cycle, defects in DNA replication, accumulation of DNA damage, and enhanced sensitivity to DNA damage agents | (68) |
| TLS | Polη | Polη is O-GlcNAcylated at T457, which promotes polyubiquitination at K462 and subsequent removal from replication forks | (75) |
| HR | Mediator of DNA damage checkpoint protein 1 (MDC1) | MDC1 is O-GlcNAcylation during DDR O-GlcNAcylation of MDC1 is increased upon irradiation |
(73) (79) |
| HR | CtIP, BRCA1 | CtIP and BRCA1 became increasingly O-GlcNAcylated after irradiation The chromatin underwent reorganization upon modulating O-GlcNAcylation |
(79) |
| HR | AND-1 | AND-1 is O-GlcNAcylated at S575 and S893, which affects the recruitment of AND-1 and CtIP to DDR sites and regulates radioresistance in colorectal cancer cells | (112) |
| HR | YTHDC1 | YTHDC1 is O-GlcNAcylated at S396 upon DDR, which promotes recruitment of YTHDC1 to DDR sites and YTHDC1–m6A binding. It enhances YTHDC1–m6A condensate formation, Rad51 focus formation, and HR | (88) |
| HR and NHEJ | Histone H2B | H2B S112 O-GlcNAcylation increased upon DSB, which promotes HR and NHEJ by binding with NBS1 and enhances NBS1 IRIF formation | (83) |
| NHEJ | DNA-PK | DNA-PKcs O-GlcNAcylation promotes its kinase activity and antagonizes bleomycin-induced Ser2056 phosphorylation | (91) |
| NHEJ | NONO and Ku70/80 | NONO and Ku70/80 are recognized by the pseudo HAT domain of OGA for deglycosylation, which is required for NONO dissociation from the chromatin and degradation | (76) |
| CDK9 inhibitor–induced DNA damage in castration-resistant prostate cancer (CRPC) | Mre11 | OGT and MRE11 are essential for the repair of CDK9 inhibitor–induced DNA damage. Mechanistically, OGT is required for MRE11 chromatin loading in cells treated with CDK9 inhibitor. MRE11 and O-GlcNAc are enriched at the prostate cancer–specific small nucleotide polymorphic sites | (84) |
| Error-prone DDR pathway | HMGB1 | HMGB1 is O-GlcNAcylated at S100 in human non–small-cell lung carcinoma cells. O-GlcNAc reduces the ability of HMGB1 to facilitate DNA repair, resulting in error-prone processing of damaged DNA. Mechanistically, O-GlcNAc enhances HMGB1 oligomerization on linear, nucleosomal, supercoiled, cruciform, and interstrand cross-linked damaged DNA structures | (105) |