Table 3.
O-GlcNAcylated proteins during the DNA damage response.
| Protein name | Molecular mechanisms | References |
|---|---|---|
| Histone H2AX (H2AX) | H2A is O-GlcNAcylated at T101 at basal levels, and at S139 upon DDR. | (96) |
| Histone 2B (H2B) | DSBs induce O-GlcNAcylation at S112 of H2B, leading to its binding with Nijmegen breakage syndrome 1 (NBS1), mediating focus formation of NBS1 and subsequent homologous recombination (HR) and nonhomologous end-joining (NHEJ) | (97) |
| Histone 2A (H2A) | Camptothecin (CPT) or Etoposide (ETP) induces O-GlcNAcylation at S40 of H2A, which coIPs with acetylated H2AZ and γH2AX. O-GlcNAcylated H2AS40 localizes to DNA damage sites. Its aberration prevents recruitment of DNA-PKcs and Rad51. | (98, 99) |
| Ataxia-telangiectasia mutated (ATM) | In HeLa and primary neuron cells, ATM interacts with OGT and is O-GlcNAcylated. O-GlcNAcylation enhances X-ray induced ATM activation at S1981. | (100) |
| In mouse embryonic fibroblasts (MEFs), OGT deletion upregulates ATM activation at S1987. | (20) | |
| DNA-dependent protein kinase (DNA-PK) | DNA-PK is O-GlcNAcylated, and this modification increases upon ER stress, but not upon oxidative stress, osmotic stress, or double-strand breaks (DSBs). | (101) |
| Mediator of DNA damage checkpoint protein 1 (MDC1), | O-GlcNAcylation of H2AX suppresses its expansion on chromatin during DDR. MDC1 is O-GlcNAcylated upon DDR, which antagonizes its phosphorylation. | (96) |
| Polη | O-GlcNAcylation at T457 of Polη promotes CRL4CDT2-dependent Polη polyubiquitination at K462 and subsequent p97-dependent removal from replication forks, ensuring translesion DNA synthesis (TLS) | (32) |