refinements and new terms for mitotic chromosome segregation

[ValWood]

GO:0007080 Name mitotic metaphase plate congression Definition The cell cycle process in which chromosomes are aligned at the metaphase plate, a plane halfway between the poles of the mitotic spindle, during mitosis.

This seems to consist of 2 broad steps

1) new term request microtubule plus-end directed mitotic chromosome migration lateral attachment and migration of the mitotic sister chromatids along a monopolar spindle microtubule towards the plus end

synonym exact plus-end directed chromosome gliding fig 5 c in PMID:26256832) narrow dynein/CENP-E mediated lateral attachment (fig1 new Review A Centromere-Signaling Network Underlies the Coordination among Mitotic Events PMID: 26705896) this is narrow because the gene products seem to be different in different orgs, not direct orthologs (different kinesin family members)

2) GO:0051315 attachment of mitotic spindle microtubules to kinetochore The cell cycle process in which spindle microtubules become physically associated with the proteins making up the kinetochore complex during mitosis. During mitosis, the kinetochores of sister chromosomes are situated facing opposite spindle poles and bipolar attachment of the sister chromosomes to the spindle occurs.

redefine this to make it clear that this refers to Ndc80 complex- mediated ‘end-on’ attachment (fig1 new Review A Centromere-Signaling Network Underlies the Coordination among Mitotic Events PMID: 26705896)

so perhaps The process in which the kinetochores become physically attached to the mitotic spindle microtubules
of opposing spindle poles by end on attachment, mediated by the Ndc80 complex and other factors? exact synonym Ndc80 complex- mediated ‘end-on’ attachment (or maybe this could be the primary term name)

Note: Ndc80 complex is conserved in all eukaryotes http://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0031262

Or maybe the existing term should be a parent and we need two new terms?

Also consider this at the same time. https://github.com/geneontology/go-ontology/issues/11674 maybe the biorientation term represents the end-on attachment.....

[ValWood]

this is a nice schematic summary from the review

[ValWood]

refinement new term request microtubule plus-end directed mitotic chromosome migration The process whereby mitotic sister chromatids are laterally attached to a spindle microtubule and migrate in a microtubule plus end direction to the equator of the spindle

[mah11]

better still (more consistent with wording and hyphenation of existing terms):

name: plus-end-directed mitotic chromosome movement along microtubule def: "The cell cycle process in which chromosomes that are laterally attached to one or more mitotic spindle microtubules migrate towards the spindle equator via plus-end-directed movement along the microtubules."

[mah11]

tangential note: I spotted that the GO:0007079 def wording is funny - I think "This mediates by" should be "This is mediated by".

[dosumis]

Seems to be overlapping with / mitotic version of:

[ValWood]

This is the next step ( I think this is describing movement after separation, ie cohesin destruction). All of the ones above are related to biorientation and alignment (all before cohesin destruction). In my request the chromosomes are moving away from the spindle poles towards the equator...

They are related in that they both represent microtubule-based movement of chromosomes.

[dosumis]

Typo on this: PMID:26256832 (=Liver resection after selective internal radiotherapy (SIRT): Proof of concept, initial survival, and safety.)

Got it: PMID:26258632

[dosumis]

Finally grokking this (I think)

First the chromosomes attach laterally and migrate (glide) via the action of motor proteins, towards the plus end/spindle equator/congression plate. Then they form stable, correctly oriented, end-on connections to the spindle microtubules, separate, and get pulled towards the spindle polls by microtubule shortening.

Correct?

If it is safe to assume biorientation is end-on, then we can have:

mitotic metaphase plate congression . <- po attachment of mitotic spindle microtubules to kinetochore . . <- is_a: NEW: lateral attachment of mitotic spindle microtubules to kinetochore . . <- is_a: sister chromatid biorientation . <- po NEW: microtubule plus-end directed mitotic chromosome migration

attachment of mitotic spindle microtubules to kinetochore: The cell cycle process in which spindle microtubules become physically associated with the proteins making up the kinetochore complex as part of mitotic metaphase plate congression. [PMID:26258632, PMID:26705896] comment: This class covers transient, lateral attachment to microtubules as well as stable, correctly oriented, end-on attachment (biorientation)

lateral attachment of mitotic spindle microtubules to kinetochore: The cell cycle process in which sister chromatids become laterally attached to spindle microtubules as part of mitotic metaphase plate congression. Attachment precedes migration along microtubules towards the spindle equator (metaphase plate). [PMID:26258632, PMID:26705896]

microtubule plus-end directed mitotic chromosome migration: The cell cycle process in which chromosomes that are laterally attached to one or more mitotic spindle microtubules migrate towards the spindle equator via plus-end-directed movement along the microtubules. This process is part of mitotic metaphase plate congression. [PMID:26258632, PMID:26705896] synonym: plus-end directed chromosome gliding EXACT [PMID:26258632]

sister chromatid biorientation: The cell cycle process in which sister chromatids establish stable, end-on attachments to the plus ends of microtubules emanating from opposite spindle poles, oriented such that separation can proceed. This is the final step of metaphase plate congression. [PMID:26258632, PMID:26705896] synonym: plus-end attachment of mitotic spindle microtubules to kinetochore(SCOPE???)

[ValWood]

David First the chromosomes attach laterally and migrate (glide) via the action of motor proteins, towards the plus end/spindle equator/congression plate. Then they form stable, correctly oriented, end-on connections to the spindle microtubules, separate, and get pulled towards the spindle polls by microtubule shortening.

Correct?

Yes-

• At least that's my understanding but I only grasped all of this recently! now it all makes sense to me (I have annotated about 100 chromosome segregation papers last year, so I don't know why it took me so long.... probably because the papers all deal with such small parts of the overall process and I only just assembled it in my head).

I think your terms sound good. I think it is safe to assume that biorientation is end-on attachment. However, chromosome microtubule attachment isn't always part of congression (chromosomes are still attached to the microtubules when they move towards the spindle poles in anaphase), so I think this parent will need moving out.

I will check the definitions with Yoshi Watanabe who authored the paper I am curating. ......

[dosumis]

However, chromosome microtubule attachment isn't always part of congression (chromosomes are still attached to the microtubules when they move towards the spindle poles in anaphase), so I think this parent will need moving out.

OK. Will move.

[dosumis]

Fixed as outlined above.

[ValWood]

Yep its complaint with this too https://en.wikipedia.org/wiki/Kinetochore The end-on attachment if definitely considered part of 'congression'

Maybe also extend the mitotic congression def in some way to give "start and end"

"Congression begins when chromosomes start to move along spindle microtubules towards the bipolar spindle equator, and ends when all chromosomes have end-on microtubule attachment to opposite spindle pole bodies.

[ValWood]

Hi David, Should see these terms yet? Val

[ValWood]

Hi David,

I think these terms are in but some tweaking might be required.

mitotic sister chromatid biorientation Ontology Biological Process Current Definition The cell cycle process in which chromosomes that are laterally attached to one or more mitotic spindle microtubules migrate towards the spindle equator via plus-end-directed movement along the microtubules. This process is part of mitotic metaphase plate congression.

This is defined as "lateral attachment' but is achieved by the stable end-on attachment of the microtubule to the spindle.

I think it might be clearer if this were named "attachment of kinetochore to mitotic spindle microtubule plus end" exact synonym "end-on chromosome-microtubule attachment involved in mitosis" exact synonym "biorientation'

[dosumis]

Ughh, sorry. I think the one of the defs ended up on the wrong term. Occasionally happens in Protege if you move focus while editing a term. Sorry. Correcting now.

[ValWood]

I thought it looked like a "technical" glitch ;)

[ValWood]

Hi David,

mitotic sister biorientation still says "laterally' in QuickGO in case this slipped through the cracks