NTR: [protein-RNA covalent cross-linking repair] [protein-DNA covalent cross-linking activity]

[sylvainpoux]

Hi GO, I would need 2 new terms related to protein-nucleic acid cross-linking.

Thanks

Sylvain

The first term is pretty easy and is related to the resolution of protein-RNA covalent cross-links that cause ribosome stalling. The definition is very similar to existing protein-DNA covalent cross-linking repair

1) Term: :protein-RNA covalent cross-linking repair Category: Process Definition: The removal of covalent cross-link between RNA and a protein. Protein-RNA covalent cross-links cause translation stress by stalling elongating ribosomes. PMID:37951215 PMID:37951216 Child of GO:0072344 rescue of stalled ribosome

2) I would also need a term for the enzyme that mediates the protein-DNA covalent cross-linking activity, a kind of suicide enzyme that recognizes abasic sites, and creates a protein-DNA covalent cross-link that will be degraded.

Term: protein-DNA covalent cross-linking activity Category: Molecular function Definition: Catalysis of the cross-link between a protein and a DNA abasic site, forming a thiazolidine linkage between a DNA ring-opened abasic site and the alpha-amino and sulfhydryl substituents of cysteine residue of the protein. PMID:30554877, PMID:31235913 Xref: there is a reaction in MetyCyc: RXN-21016 child of GO:0016829 lyase activity

PMID:30554877, PMID:31235913 Xref: there is a reaction in MetyCyc: RXN-21016 child of GO:0016829 lyase activity

[raymond91125]

I wonder if protein-RNA covalent cross-linking repair is more appropriately placed as a child of GO:0042245 RNA repair. DEF: "Any RNA repair process that removes covalent cross-link between RNA and a protein. Protein-RNA covalent cross-links cause translation stress by stalling elongating ribosomes."

[sylvainpoux]

Hi @raymond91125, No, it is not related to RNA repair since cross-linked RNA will probably be destroyed with the cross-linked protein. If you read the articles you will see that the process is really to rescue stalled ribosomes. Thanks Sylvain

[raymond91125]

+[Term] +id: GO:0160127 +name: protein-RNA covalent cross-linking repair +namespace: biological_process +def: "A process that rescues stalled ribosomes by removing the covalent cross-link between RNA and a protein." [PMID:37951215, PMID:37951216] +is_a: GO:0072344 ! rescue of stalled ribosome +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/26415" xsd:anyURI +created_by: rynl +creation_date: 2023-11-27T19:54:13Z

[raymond91125]

There is a BP term GO:0018142 protein-DNA covalent cross-linking with 3 specific AA types as children (no annotations). HMCES has been annotated with that term. Should we retire the BP terms? @sylvainpoux Of the 3 gp annotated (HMCES, yedK, Gcna), Gcna is actually involved in resolving DNA-protein crosslinks and is annotated with GO:0106300 protein-DNA covalent cross-linking repair.

[sylvainpoux]

Hi @raymond91125, No, we should keep this term because other proteins are involved in this process, such as FANCJ (see https://www.ebi.ac.uk/internal-tools/protein2go/dynamic.html?database=production#ac=Q9BX63) or RFWD3 Thanks Sylvain

[raymond91125]

Hi @raymond91125, No, we should keep this term because other proteins are involved in this process, such as FANCJ (see https://www.ebi.ac.uk/internal-tools/protein2go/dynamic.html?database=production#ac=Q9BX63) or RFWD3 Thanks Sylvain

I cannot access that link.

[sylvainpoux]

Hi @raymond91125, In theory you should be able to access protein2GO, I don't know why it doesn't work Anyway, I annotated this BP term to other proteins, it is why we should keep this BP term Thanks Sylvain

[raymond91125]

I can only access this page https://www.uniprot.org/uniprotkb/Q9BX63 I could not find annotations with GO:0018142 protein-DNA covalent cross-linking. Could you give me the reference so that I can understand the difference between single-step MF protein-DNA covalent cross-linking activity vs. BP? Thanks.

[sylvainpoux]

The reference isthe following: PMID:36608669 FANCJ promotes protein-DNA covalent cross-linking: "Involved in the repair of abasic sites at replication forks by promoting the degradation of DNA-protein cross-links: acts by catalyzing unfolding of HMCES DNA-protein cross-link via its helicase activity, exposing the underlying DNA and enabling cleavage of the DNA-protein adduct by the SPRTN metalloprotease (PubMed:16116421, PubMed:36608669)."

By the way, this information was mentioned in articles I provided in the original submission

Sylvain

[raymond91125]

@sylvainpoux SPRTN is already annotated with GO:0106300 protein-DNA covalent cross-linking repair and so should be FANCJ. But I thought we are talking about the formation, thus the term GO:0018142 protein-DNA covalent cross-linking. I don't see evidence for a multi-gene process involved in the formation of the crosslink but a single gene product like HMCES/yedK and perhaps topoisomerases (PMID:35303790)

[raymond91125]

The formation of DPC by topoisomerases is an intermediate step in its normal function. Thus I'm not sure it should be associated with the proposed MF term "protein-DNA covalent cross-linking activity". But if we do include them, the proposed definition should be revised accordingly.

[sylvainpoux]

Hi @raymond91125 yes, you are right, let's deprecate the GO:0018142 protein-DNA covalent cross-linking, I will replace it with the new MF protein-DNA covalent cross-linking activity when it is created. Thanks for pointing this out Sylvain

[raymond91125]

+[Term] +id: GO:0160129 +name: protein-DNA covalent cross-linking activity +namespace: molecular_function +def: "Catalysis of the cross-link between a protein and a DNA abasic site, forming a thiazolidine linkage between a DNA ring-opened abasic site and the alpha-amino and sulfhydryl substituents of cysteine residue of the protein." [PMID:30554877, PMID:31235913] +xref: MetaCyc:RXN-21016 +is_a: GO:0016829 ! lyase activity +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/26415" xsd:anyURI +created_by: rynl +creation_date: 2023-12-06T17:33:59Z