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OGA is associated with deglycosylation of NONO and the KU complex during DNA damage repair.
- Source :
-
Cell death & disease [Cell Death Dis] 2021 Jun 16; Vol. 12 (7), pp. 622. Date of Electronic Publication: 2021 Jun 16. - Publication Year :
- 2021
-
Abstract
- Accumulated evidence shows that OGT-mediated O-GlcNAcylation plays an important role in response to DNA damage repair. However, it is unclear if the "eraser" O-GlcNAcase (OGA) participates in this cellular process. Here, we examined the molecular mechanisms and biological functions of OGA in DNA damage repair, and found that OGA was recruited to the sites of DNA damage and mediated deglycosylation following DNA damage. The recruitment of OGA to DNA lesions is mediated by O-GlcNAcylation events. Moreover, we have dissected OGA using deletion mutants and found that C-terminal truncated OGA including the pseudo HAT domain was required for the recruitment of OGA to DNA lesions. Using unbiased protein affinity purification, we found that the pseudo HAT domain was associated with DNA repair factors including NONO and the Ku70/80 complex. Following DNA damage, both NONO and the Ku70/80 complex were O-GlcNAcylated by OGT. The pseudo HAT domain was required to recognize NONO and the Ku70/80 complex for their deglycosylation. Suppression of the deglycosylation prolonged the retention of NONO at DNA lesions and delayed NONO degradation on the chromatin, which impaired non-homologus end joining (NHEJ). Collectively, our study reveals that OGA-mediated deglycosylation plays a key role in DNA damage repair.
- Subjects :
- Antigens, Neoplasm genetics
Cell Line, Tumor
Cell Nucleus genetics
Cell Nucleus radiation effects
Cell Proliferation
DNA-Binding Proteins genetics
Glycosylation
HEK293 Cells
Histone Acetyltransferases genetics
Humans
Hyaluronoglucosaminidase genetics
Ku Autoantigen genetics
Protein Domains
RNA-Binding Proteins genetics
Substrate Specificity
Antigens, Neoplasm metabolism
Cell Nucleus enzymology
DNA Damage
DNA End-Joining Repair
DNA-Binding Proteins metabolism
Histone Acetyltransferases metabolism
Hyaluronoglucosaminidase metabolism
Ku Autoantigen metabolism
Protein Processing, Post-Translational
RNA-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 12
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 34135314
- Full Text :
- https://doi.org/10.1038/s41419-021-03910-6