Taxon constraint: TreeGrafter motivated DNA demethylase related

[ValWood]

Please provide as much information as you can:

• GO term ID label:

GO:0035516 broad specificity oxidative DNA demethylase activity IEA with PTHR16557:SF2 GO:0035552 oxidative single-stranded DNA demethylation IEA with PTHR16557:SF2

Yeast (at least fission yeast) does not have DNA methylation (hence demethylation) These mappings were applied to a tRNA demethylase

@pgaudet if GO:0035552 will eventually be obsoleted I can add a do_not_annotatae tag to that branch instead

• Request to add a taxon constraint:

• • only in taxon:
• • never in taxon:

• Request to remove a taxon constraint: Please specify

• Supporting evidence if available (e.g PMID):

[pgaudet]

I just obsoleted the BP, see https://github.com/geneontology/go-ontology/issues/26935

What's wrong with the MF ?

[ValWood]

OK I didn't see that, I just spotted it by chance because I saw it under the alkylation term.

The MF will still need restricting for yeast (yeast does not have DNA methylation)

[pgaudet]

Yeast (at least fission yeast) does not have DNA methylation (hence demethylation)

maybe not DNA, but RNAs are methylated, aren't they? https://www.nature.com/articles/s41467-021-23457-6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526270/

[pgaudet]

DAN demethylases can act in DNA repair; are you sure this is not happening in yeast?

[ValWood]

Oh good point yes. The annotation is still a problem though because it is being applied by TreeGrafter to an RNA demethylase:

https://www.pombase.org/gene/SPBC13G1.04c

[ValWood]

right I see https://www.uniprot.org/uniprotkb/Q13686/entry All the evidence points to this being a tRNA demethylase physiologically with a role to demethylate DNA as part of silencing Specifically demethylates DNA methylated on the 6th position of adenine (N6-methyladenosine) DNA (PubMed:30392959, PubMed:30017583). N6-methyladenosine (m6A) DNA is present at some L1 elements in embryonic stem cells and probably promotes their silencing (By similarity). Demethylates mRNAs containing N3-methylcytidine modification (PubMed:31188562).

the role in repair appears to be negligible from historical papers:

Also able to repair alkylated single-stranded DNA by oxidative demethylation, but with low activity (PubMed:18603530).

the non repair role is supported in fission yeast https://www.pombase.org/reference/PMID:22365419

[pgaudet]

Still, we have a NOT annotation to the MF in PAINT to this gene:

@alexsign @thomaspd @huaiyumi Why is this being overridden by TreeGrafter?

[pgaudet]

So, we need to remove the NOT annotation?

[ValWood]

No the NOT annotation is correct, it isn't a DNA demethylase, or involved in repair, it's a

tRNA N1-methyladenine (m1A58) demethylase (I believe this is true across all species), but the pombe annotation comes from human.

No DNA demethylase activity has been detected in yeast: The fission yeast Schizosaccharomyces pombe has two AlkB homologs and here we have addressed the function of one of these, Abh1, which appears not to possess a classical AlkB-like repair activity. No enzymatic activity was found toward methylated DNA or etheno adducts, nor was the yeast abh1- mutant sensitive toward alkylating agents. Interestingly, heterologous expression of E. coli AlkB protected the fission yeast cells from alkylation induced cytotoxicity, suggesting that S. pombe lacks systems for efficient repair of lesions that are AlkB substrates. Further, we show that Abh1 possesses an unexpected DNA incision activity at apurinic/apyrimidinic (AP) sites. This AP lyase activity did not depend on 2OG and Fe(II) and was not repressed by dioxygenase inhibitors. Survival and complementation analyses failed to reveal any biological role for AP lyase cleavage by Abh1. It appears that in vitro AP lyase activity can be detected for a number of enzymes belonging to structurally and functionally unrelated families, but the in vivo significance of such activities may be questionable.

and all of the work in the last few years shows that it is a tRNA N1-methyladenine (m1A58) demethylase with a role in regulating translation https://www.uniprot.org/uniprotkb/Q13686/entry