H2A O-GlcNAcylation at serine 40 functions genomic protection in association with acetylated H2AZ or γH2AX
Bibliographic record
Abstract
BACKGROUND: We have previously reported a novel O-GlcNAc modification at serine 40 (S40) of H2A (H2AS40Gc). S40-type H2A isoforms susceptible to O-GlcNAcylation are evolutionarily new and restricted to the viviparous animals; however, the biological function of H2AS40Gc is largely unknown. H2A isoforms are consisted of S40 and alanine 40 (A40) type and this residue on H2A is located in the L1 of the globular domain, which is also known as a variable portion that distinguishes between the canonical and non-canonical H2A variants. In this study, by considering the similarity between the S40-type H2A and histone H2A variants, we explored the function of H2AS40Gc in mouse embryonic stem cells (mESCs). RESULTS: We found several similarities between the S40-type H2A isoforms and histone H2A variants such H2AZ and H2AX. mRNA of S40-type H2A isoforms (H2A1 N and H2A3) had a poly(A) tail and was produced throughout the cell cycle in contrast to that of A40-type. Importantly, H2AS40Gc level increased owing to chemical-induced DNA damage, similar to phosphorylated H2AX (γH2AX) and acetylated H2AZ (AcH2AZ). H2AS40Gc was accumulated at the restricted area (± 1.5 kb) of DNA damage sites induced by CRISPR/CAS9 system in contrast to accumulation of γH2AX, which was widely scattered. Overexpression of the wild-type (WT) H2A3, but not the S40 to A40 mutation (S40A-mutant), protected the mESC genome against chemical-induced DNA damage. Furthermore, 3 h after the DNA damage treatment, the genome was almost recovered in WT mESCs, whereas the damage advanced further in the S40A-mutant mESCs, suggesting functions of H2AS40Gc in the DNA repair mechanism. Furthermore, the S40A mutant prevented the accumulation of the DNA repair apparatus such as DNA-PKcs and Rad51 at the damage site. Co-immunoprecipitation experiment in WT and S40A-mutant mESCs revealed that H2AS40Gc physiologically bound to AcH2AZ at the initial phase upon DNA damage, followed by binding with γH2AX during the DNA damage repair process. CONCLUSIONS: These data suggest that H2AS40Gc functions to maintain genome integrity through the DNA repair mechanism in association with AcH2AZ and γH2AX.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".