Fanconi anemia pathway

[gocentral]

Hello,

Here is a new term that I would need: Fanconi anemia pathway (for review please see PMID:20713514) As child of response to DNA damage stimulus GO:0006974 also related to Fanconi anaemia nuclear complex GO:0043240

We have a new release coming up and would appreciate to have this term as soon as possible.

Thank you very much for your help, Nevila Hyka-Nouspikel

Reported by: nnouspikel

Original Ticket: geneontology/ontology-requests/9888

[gocentral]

• assigned_to: rfoulger --> jl242

Original comment by: jl242

[gocentral]

• priority: 5 --> 8

Original comment by: jl242

[gocentral]

To follow up on my previous request: The Fanconi Anemia pathway coordinates a complex mechanism that enlists elements of three classic DNA repair pathways, namely homologous recombination, nucleotide excision repair, and mutagenic translesion synthesis, in response to genotoxic insults. Fanconi Anemia pathway employs a unique nuclear protein complex that ubiquitinates FANCD2 and FANCI, leading to formation of DNA repair structures. We can use the above definition given in the abstract of PMID:19686080. Allan D’Andrea is the expert in the field. Let me know if this sounds ok.

Nevila

Original comment by: nnouspikel

[gocentral]

As far as I know, Fanconi anemia is caused by mutations in any of a number of genes (about 14 so far?) whose products form and regulate a complex involved in DNA repair. The exact role of the complex remains to be defined in molecular detail.

If this is right, then perhaps "Fanconi anemia pathway" could be made some kind of synonym for an existing DNA repair process term at the appropriate level of granularity. (I expect that disease phenotype terms, especially ones for diseases that arise due to disruption of any one of several normal processes, do not fit well into GO).

Peter

Original comment by: deustp01

[gocentral]

Hi Peter,

Thanks for your answer.

Fanconi anemia pathway operates under physiological conditions. Dysfunction of this pathway causes a disease known as Fanconi anemia, hence the name of the pathway. It is a DNA damage response pathway which activates several DNA repair pathways, but it is not a DNA repair pathway in itself. Regulation of FA pathway is described in a recent review (PMID:19686080, Fig 3). Of course one can use GO:0006974 -response to DNA damage stimulus, but it would be nice to go more specific given that this pathway is the subject of a considerable amount of papers.

Nevila

Original comment by: nnouspikel

[gocentral]

I agree with Peter, , (included mre11 complex and FANCM-MHF Slx1-4 complex), and the pathways seems to be replication fork processing, possibly resolution of recombination intermediates)... We do not generally add pathway generally terms (except for signalling pathway) without defining the process. I agree with Peter, this should be a synonym of an existing term, (but it could span more than one process).

Nevila How would you define the term?

Val

Original comment by: ValWood

[gocentral]

Hi Val, Here is my definition: Fanconi anemia pathway is a nuclear signaling pathway which is activated by DNA lesions, mainly interstrand DNA crosslinks that cause replication fork stalling during S-phase. It triggers crosslink repair by coordinating activities of nucleotide excision repair, translesion synthesis, and homologous recombination (PMID:20965415/ PMID:19686080).

Looking forward to your decision. Thanks, Nevila

Original comment by: nnouspikel

[gocentral]

Hi - I think the complex term is fine, I'll add that.

For the process term I'm in two minds. It's almost like a process inferred by a mutant phenotype - we know what disruption of the pathway causes but not the exact mechanism by which the pathway operates.

That said, there are a lot of papers about this pathway and some molecular details are known. We add signalling pathways knowing a lot less about them. It seems like a 'meta' pathway, activating downstream DNA repair processes so it would be hard to add synonyms to other terms because it isn't really synonymous.

I'll take it to our next editors meeting, see what the others think.

Original comment by: jl242

[gocentral]

Thanks Jane.

Original comment by: nnouspikel

[gocentral]

Oh I see the complex term already exists - I ignore my first point below then!

Original comment by: jl242

[gocentral]

• assigned_to: Jane Lomax --> David Osumi-Sutherland

Original comment by: paolaroncaglia

[gocentral]

Hi Nevila,

Apologies, this request fell through the cracks due to a malfunctioning in the SF tracker system. Please let us know if you still need the signaling pathway term. If so, I'm assigning this ticket to David OS, as he's 'inherited' signaling requests after Becky and Jane left the EBI.

Thanks,

Paola

Original comment by: paolaroncaglia

[dosumis]

Closing as we now have the complex term: Fanconi anaemia nuclear complex GO:0043240 - and the pathway term appears too controversial (see comments).