NTRs from user submission, checkpoint related

[gocentral]

I need a few new terms to process this user feedback (one day everyone will do this)

DNA binding, recombination hotspot child of DNA binding

DNA binding, transcription promoter child of sequence-specific DNA binding (some existing child terms would need grouping under here including all of htiose with 'response element?"

activation of meiotic recombination positive regulation of meiotic recombination regulation of chromatin assembly regulation of chromatin disassembly

regulation of cell cycle checkpoint in G1 (G0) see previously requested terms https://sourceforge.net/tracker/?func=detail&aid=1853360&group\_id=36855&atid=440764 would this be negative regulation of G1 to G0 transition

Happy New Year!

Reported by: ValWood

Original Ticket: "geneontology/ontology-requests/5694":https://sourceforge.net/p/geneontology/ontology-requests/5694

[gocentral]

Original comment by: ValWood

[gocentral]

File Added: wayne_wahls.doc

Original comment by: ValWood

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• assigned_to: nobody --> tairtb

Original comment by: ukemi

[gocentral]

Checkpoints. Ouch. Argh. I always cringe when checkpoints come up, because they're not straightforward in many many ways. Whinging aside, we have used the "cell cycle checkpoint" wording in term names because it's universally used by the cell cycle community; for that reason we have to keep it around in synonyms if we change term names.

That said, community usage can be a bit woolly -- a "checkpoint" usually corresponds to a point in time (relative to the whole cell cycle or a phase thereof, not absolute time elapsed), but is usually described based on events that must take place (e.g. completing DNA replication) or biological qualities established (e.g. minimum cell size reached) for the checkpoint to be passed.

Gene products said to be "involved in" a checkpoint do various things -- there's usually some signal transduction, and some form of detection or monitoring of a given process or quality. This is where I kind of fall down on specifics, but Val can consult experts if we need more details. What the gene product roles have in common is that their concerted actions determine whether the cell will proceed through the cell cycle, or delay or arrest the cycle, at a checkpoint.

I would oppose making the existing term obsolete; it would be an immensely unpopular move (at least among the yeast annotators), and wouldn't gain anything. The ambiguity and other problems can be solved by renaming and improving the definition in ways that leave the annotations accurate.

I suggest "regulation of progression through cell cycle checkpoint" (or perhaps "regulation of progression past cell cycle checkpoint"); I could live with "regulation of cell cycle at cell cycle checkpoint" if there's some reason to avoid "progression". I don't like "regulation of cell cycle checkpoint" because it doesn't do as much to clarify the what-is-a-checkpoint-anyway question.

Does that help? m

Original comment by: mah11

[gocentral]

• labels: --> New term request
• milestone: --> 224410

Original comment by: mah11

[gocentral]

I agree with all Midori's comments particularly Argh & Ouch.

I would prefer not to obsolete as these terms have been used correctly, but their defs and names could be improved.

There may be a problem where some progression through checkpoint terms have a 'signal transduction' parent GO:0000077 : DNA damage checkpoint has this parent but DNA replication checkpoint does not.

DNA damage checkpoint is described as a signal transduction pathway, where DNA damage checkpoint is described as "signal transduction based"

AS Midori said, there are esssentially 2 components to a checkpoint

i) the gene products upstream of the signal transduction pathway which do the checkpoint sensing. for example translation initiation factor eIF3i which interacts genetically with cdc2 to suppress S-M checkpoint PMID: 9560390 or single-stranded DNA binding protein Ssb2 activates the replication checkpoint PMID:9111307 or replication fork protection complex subunit Swi1 activates the replication checkpoint PMID:14560029

These gene products activate the checkpoint, mutations in them disrupt the checkpoint and cause defects in checkpoint signalling and they interact genetically with the signal transduction pathway but I don't think they are considered to be part of the 'signal transduction pathway' itself (i.e the signalling cascade which starts with the ATR checkpoint kinases for DNA damage and DNA replication checkpoints).

ii) the signal cascade itself which detects these signals and mediates the response (replication fork slowing or whatever)

perhaps the new renamed terms should have children to indicate activation of checkpoint checkpoint signalling (would have signal transduction parent)

although activation of the checkpoint would be a child wouldn't it. No its probably OK as it is, but the DNA replication/damage checkpoint parentage should probably be standardised.

see ugh....

Original comment by: ValWood

[gocentral]

We have redefined the 'cell cycle checkpoint' term to make it a more bona fide process. The new definition is: "The cell cycle regulatory process by which progression through the cycle can be halted until conditions are suitable for the cell to proceed to the next stage." This definition reflects the two parts that Val discusses below, the sensing and the signal transduction mechanism that actually halts the cell cycle.

So, based on this discussion we think that 'DNA damage checkpoint' is not defined correctly. We think the definition should be more broad to include both the signal transduction mechanism as well as the sensing process. How about "The cell cycle regulatory process by which progression through the cycle can be halted due to the sensing of DNA damage and reinitiated when conditions are suitable." We propose that the relationship between this term and signal transduction be removed. We can create a new part_of child that reflects the signal transduction process similar to 'DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest' (GO:0006977). Does this make sense? If so we will implement it.

Note that this change will affect annotations in that anything annotated to 'DNA damage checkpoint' will no longer be annotated to 'signal transduction' by transitivity.

D & T

Original comment by: ukemi

[gocentral]

Hi,

I was asked to take a look at the checkpoint portion of this sourceforge item for SGD. I agree with earlier comments by Midori and Val that making the term(s) obsolete would be very unpopular and agree that tweaking the definition and parentage would be a better way to go. I also don't favor creating regulation of checkpoint terms because checkpoint proteins are regulators so this proposal would for me at least confuse the situation.

As I understand it, the checkpoint includes sensors, signal transducers, effectors and also adaptation mechanisms (when the damage cannot be corrected). I therefore favor the proposal to redefine these terms to include the sensing, signal transduction and downstream effectors aspects of this process. I hesitate with the last bit of the definition '... and reinitiated when conditions are suitable.', since cells will eventually progress through the cell cycle after some time even if the damage cannot be repaired (adaptation mentioned above), often with deleterious consequences. If redefined I agree that the relationship between the checkpoint term(s) and signal transduction be removed and that the creation of child terms to annotate sensors, signal transducers and effectors of the checkpoint would be a logical solution. This would allow annotations to the parent term when little is known or the more granular terms where more is known. I am not sure that adaptation should be included as a child term since this is not so much part of the checkpoint process, rather due to a failure to correct a defect resulting in the cellular decision to pass through the checkpoint.

Cheers, Rob

Original comment by: rnash

[gocentral]

Thanks for your input, Rob. Would you like to have a shot at an even better definition of 'cell cycle checkpoint' that includes all of the points you mentioned? We'd be happy to have someone more expert than us work on that. We can then integrate the relevant parts of the new definition into the children terms.

Cheers,

Tanya

Original comment by: tberardini

[gocentral]

I took a quick look at a couple of papers and the existing proposed definition (much of which is fine) and tweaked it a bit although it may too wordy/specific:

"Regulatory processes that control cell cycle progression by monitoring the timing and integrity of specific cell cycle events. When condition are not suitable, a network of sensors, signal transducers, and effectors temporarily halt progression while attempts are made to correct the defect."

Cheers,

Rob

Original comment by: rnash

[gocentral]

also, while I remember, (As I am listenting to a talk on checkpoints) we should also have child terms for checkpoint maintenence. Rationale,

some genes affect checkpoint establishment only but some affect maintenence of the checkpoint (after it is established)

val

Original comment by: ValWood

[gocentral]

• summary: NTRs from user submission, the best user feedback! --> NTRs from user submission, checkpoint related

Original comment by: ValWood

[gocentral]

taking over for the final push; Val, Becky and I have been discussing checkpoints for a couple of newer items

Original comment by: mah11

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• assigned_to: tairtb --> gomidori

Original comment by: mah11

[gocentral]

now done; specifics in extensive comments on SF 3123693

https://sourceforge.net/tracker/?func=detail&aid=3123693&group\_id=36855&atid=440764

Original comment by: mah11

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• status: open --> closed-fixed

Original comment by: mah11

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• milestone: 224410 --> PomBase

Original comment by: mah11