geneontology / go-ontology

Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
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Term merge: [term labels and ID] double-strand break repair via single-strand annealing, removal of nonhomologous ends (GO:0000736) #24071

Open ValWood opened 2 years ago

ValWood commented 2 years ago

double-strand break repair via single-strand annealing, removal of nonhomologous ends (GO:0000736)

double-strand break repair via single-strand annealing

The " removal of nonhomologous ends" part of this item represents a MF term(s) (performed by nucleotide-excision repair factor 1 complex (GO:0000110)

raymond91125 commented 1 year ago

image

raymond91125 commented 1 year ago

GO:0000736 IS_A removal of nonhomologous ends, and PART_OF double-strand break repair via single-strand annealing. At the moment, GO:0000735 removal of nonhomologous ends is a BP. The term reference PMID:10357855 seems to suggest that there is an additional step involving MSH genes and thus it being a BP makes sense.

ValWood commented 1 year ago

This cited review for the term http://europepmc.org/article/MED/10357855 Says The removal of these 3′ nonhomologous tails depends on the nucleotide excision repair genes RAD1 and RAD10 (123). Rad1p and Rad10p were shown to form an endonuclease that can cleave DNA with a “flap” of 3′-end ssDNA (22, 483, 509, 510). None of the other NER genes (RAD2, RAD3, RAD7, RAD14, RAD16, and RAD25) are required (195), but in vivo, the process depends on the MSH2 and MSH3 mismatch repair genes (476)

So it seems biochemically as though it should be represented by a single MF term? Presumably MSH2 and MSH3 are sensors of damage and are causally upstream of the endonuclease step.

The parent GO:0000735 removal of nonhomologous ends Is defined "The removal of nonhomologous sequences at the broken 3' single-strand DNA end before DNA repair synthesis can occur."

Which is clearly defined as a molecular function.

The annotation should presumably be something like GO:0048257 3'-flap endonuclease activity part_of double-strand break repair via single-strand annealing

@pgaudet do you have any thoughts on this. Do these steps need to be processes?

ValWood commented 1 year ago

This term might be OK, but the parent term really does define a molecular function...

pgaudet commented 1 year ago

I put this in the future project to review the DNA repair branch. We can postpone this until we can work on this.

pgaudet commented 1 year ago

All annotations are by SGD, to endonucleases.

@srengel Do you know more about this process?

srengel commented 1 year ago

i don't mind the suggested merge, but i disagree with this statement:

"The parent GO:0000735 removal of nonhomologous ends Is defined "The removal of nonhomologous sequences at the broken 3' single-strand DNA end before DNA repair synthesis can occur."

Which is clearly defined as a molecular function."

the part i disagree with is the last bit: "Which is clearly defined as a molecular function."

wha?

ValWood commented 1 year ago

Here is the logic:

"The removal of nonhomologous sequences at the broken 3' single-strand DNA end before DNA repair synthesis can occur."

"before DNA repair synthesis can occur" is a bit strange bacause it isn't a standard differentia, it is saying when something happens, not what it is.

and the term itself is part of "double strand break repair via single strand annealing" You could effectively scrub "before DNA repair synthesis can occur." from the definition.

This leaves "The removal of nonhomologous sequences at the broken 3' single-strand DNA", which is, effectively a "DNA 3' flap endonuclease activity"..a DNA 3' flap endonuclease cleaves a non homologous 3' single-stranded sequence

I'm not sure if this process does include anything other than endonuclease activity, but if it does, it isn't explicitly stated in the definition.

and the pathway is always drawn like this:

Screenshot 2023-04-11 at 15 48 35

There are quite a few DNA repair single steps which got encoded as pro cesses when we used to do precomposed MF+BP https://github.com/geneontology/go-ontology/issues/18903