new kinetochore clustering term, possible term merge

[gocentral]

I didn't spot this term requested, but the process of kinetochore clustering already exists in GO

GO:0072766 centromere clustering at the nuclear periphery A cellular localization process in which kinetochores/centromeres are transported to or maintained in the nuclear periphery. This process is responsible for the Rabl-like configuration of chromosomes in the interphase nuclei. In fission yeast this occurs at a location near the old mitotic spindle pole body.

Some of these 'related synonyms' should probably be 'exact' related centromere-SPB clustering related kinetochore clustering at spindle pole body related kinetochore clustering at SPB related kinetochore clustering at the old mitotic spindle pole body related kinetochore localization at spindle pole body

So I guess the terms should be merged and the def refined if anything is not "common"

Reported by: ValWood

Original Ticket: geneontology/ontology-requests/10649

[gocentral]

• assigned_to: David Osumi-Sutherland

Original comment by: dosumis

[gocentral]

Hi Val,

As I understand it, PMID:23283988 describes kinetochore clustering as a step that occurs before localization to the centromeres so the new term is what I need, GO:0098587 kinetochore clustering, Def: The process by which kinetochores become localized to clusters. In Saccharomyces cerevisiae, kinetochores form a single cluster before metaphase and later in the cell cycle appear as two clusters.

GO:0072766 centromere clustering at the nuclear periphery would be a step that occurs after the kinetochores have clustered. I agree some of those additional term defs related to loclization could be cleaned up.

Original comment by: dinglis

[gocentral]

Hi Diane,

Are you sure? kinetochore capture and chromosome bipolar attachment both occur after the kineochores are attached to the centromeres. In pombe (and I presumed in all other euks), the kinetochore builds up sequentially over the centromeric heterochromatin, so it never exists as a complex when it is not attached to the centromere? Bipolar attachment of the centromere/kinetochore to the spindle occurs later. So I suspect when the authors refer to kinetochore clustering they are referring to the same process.

Original comment by: ValWood

[gocentral]

Hi Val,

From PMID:23283988 they say "the molecular mechanism for kinetochore clustering during other cell cycle stages and the biological function of this clustering remain unclear."

"Our data indicate that the Slk19-mediated kinetochore clustering is likely independent of the microtubules that connect kinetochores to the spindle poles."

Our observation that Slk19 directly interacts with itself supports a possibility that Slk19 dimerization mediates kinetochore–kinetochore interaction and clustering, which likely facilitates kinetochore capture and chromosome bipolar attachment.

All of the above sound to me like kinetochore-kinetochore interactions mediate clustering which then captures centromeres. It would be good to clarify these details.

Did you look at PMID:23283988?

Diane

Original comment by: dinglis

[gocentral]

I looked at the paper. I don't think they are saying this.

The kinetochores definitely only exist as part of the centromere see http://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0000776

the "capture" referred to is the microtubules capturing the chromosomes at mitosis. I spoke to Midori and this order of events seems to be well established. I suspect these is a similar (or the same) phenonema.

val

Original comment by: ValWood

[gocentral]

Hi all,

I'm certainly no expert on any of this, but from reading around a little, I'm convinced by Val's argument here (although I can see how the ref'd article might easily be mis-read - it initially gave me the wrong impression).

Also: GO asserts that all kinetochores are part of a chromosome. This is consistent with the Wikipedia article on kinetochores and the references therein. From a little reading around, I think that we should record the stronger assertion that kinetochores are always part of some 'centromeric region of chromosome'. (The definition of this term deals with the potentially tricky issue of holocentric chromosomes: "The region of a chromosome that includes the centromeric DNA and associated proteins. In monocentric chromosomes, this region corresponds to a single area of the chromosome, whereas in holocentric chromosomes, it is evenly distributed along the chromosome.")

Given this, it must be true that kinetochore clustering cannot occur without centromere clustering.

But before I merge the terms - I need to know if clustering of kinetochores/centromeres always occurs at the nuclear periphery, or if this is just in some organisms. If the latter, then we need a general term 'centromere clustering' that is a parent class of "centromere clustering at the nuclear periphery". If the former is correct, then I'll merge. I'm now reading around now to try to ascertain this, but please yell if you know the answer.

Cheers, David

Original comment by: dosumis

[gocentral]

Earlier today I was trying to find a cartoon or 'model' to show this, but I can't find anything which shows the kinetochore clustering stage simultaneously with the chromosome arrangment. However Diane, if you look at any cartoon showing chromosome segregation, and when the 'kinetochore capture' occurs, I am sure this will all make sense. I remember I had a similar problem processing the order of events in my head when we did the pombe GO terms and phenotypes.

Do the cerevisiae kinetochores cluster near the spindle pole body as they do in pombe? This would indicate that they also localize to the nuclear periphery in interphase

Original comment by: ValWood

[gocentral]

Hi Val,

PMID:23283988 includes this statement "Because kinetochores form clusters when they are away from spindle poles, kinetochore protein(s) is likely responsible for this clustering."

This suggests to me that they do both, form at SPBs and away from SPBs.

Diane

Original comment by: dinglis

[gocentral]

actually that would be the same for fission yeast. The clusters form at the SPB, but then move they stay clustered and migrate (I think they are maybe saying that the SPB is not responsible for the clustering, even though it begins here)...although in fission yeast there are specific SPB/nuclear envelope proteins involved in the clustering.

Which cerevisiae proteins are being annotated to this term again?

Original comment by: ValWood

[gocentral]

The paper is on Slk19

Original comment by: dinglis

[gocentral]

I found another cerevisiae paper http://www.ncbi.nlm.nih.gov/pmc/articles/PMC145434/ and refs therein Owing to the clustering of the centromeres over most parts of the cell cycle (Jin et al., 2000), kinetochore proteins are observed by immunofluorescence as one or two dots per cell, located close to the nuclear side of the SPB represented by the γ-tubulin complex (Goshima and Yanagida, 2000).

David, I'm, not sure if we need the non nuclear parent process though, because the clustering occurs at the SPB, and then persists. I don't know if there is a separate annotatable process for the clustering during mitosis which is not covered by the existing term?

Note that, at present our annotations are only to the FYPO phenotype term "abnormal clustering of kinetochores to spindle pole bodies" as we are not sure at present whether there is enough information to indicate a direct or indirect role in this process for these mutants (the GO term was requested to provide formal defs for the FYPO term).

val

Original comment by: ValWood

[gocentral]

Damn we don't have a pombe /cerevisaie ortholog annotated for slk19. That's unusual. I'll see if I can turn one up...

Original comment by: ValWood

[gocentral]

Wow exciting. This looks like it could be pombe alp7 (human centrosomal transforming acidic coiled-coil (TACC) protein ortholog Alp7)

Until now I could never find a cerevisiae ortholog of this protein, but there is a conserved domain which is present in http://pfam.sanger.ac.uk/family/PF12709#tabview=tab1

Needs some work on the Pfam families to pull it all together (I'll get them to take a look), unless the Pfam is a false positive.

Very interesting.....

To be on the safe side I think I would go with a general kinetochore clustering term....

Original comment by: ValWood

[gocentral]

Hi David,

When you look at this, could you also consider parantages as this would make centromere clustering at nuclear periphery aks centromere-kinetochore clustering

a child of kinetochore localization

This came up in our phenotype term tracker: pombase:fission-yeast-phenotype] #1342 MP: poss FYPO:0001779 - abnormal centromere clustering at nuclear periphery

Midori mentions: One thing for the GO eds to consider is whether centromeres cluster at times when they don't have kinetochores assembled on them. If so, they may want a new term.

Original comment by: ValWood

[gocentral]

"Midori mentions: One thing for the GO eds to consider is whether centromeres cluster at times when they don't have kinetochores assembled on them. If so, they may want a new term."

According to Wikipedia: "(the) inner kinetochore, which is tightly associated with the centromere DNA, [is] assembled in a specialized form of chromatin persistent throughout the cell cycle." From this it looks like centromeres always have at least an inner kinetochore. So, centromere clustering must always result in kinetochore clustering.

Re: Is centromere clustering always at the nuclear periphery? I found these two papers describing centromere clustering during Drosophila meiosis.

http://www.ncbi.nlm.nih.gov/pubmed/22036181 http://www.ncbi.nlm.nih.gov/pubmed/22036182

It is not clear that clustering in these cases is at the nuclear periphery.

So, I suggest:

centromere clustering (synonym: kinetochore clustering) <- renamed from kinetochore clustering . .is_a centromere clustering at nuclear periphery

Original comment by: dosumis

[gocentral]

sounds good!

Original comment by: ValWood

[gocentral]

• status: open --> closed-fixed

Original comment by: dosumis

[gocentral]

Fixed as outlined in my last comment here (did it last week, but forgot to close ticket).

Original comment by: dosumis