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cohesin unloading/

Open ValWood opened this issue 2 years ago • 21 comments

Although this might seem counterintuitive, I am not sure that "cohesin unloading" should be under "negative regulation of cohesion" but under cohesion. The cohesion cycle process would include both loading and unloading

fix open ticket_cohesin unloading parent

(Currently this ends up in the "regulation" bin which seems odd.

Would be good to have @colinlog input next time we chat.

ValWood avatar May 25 '22 14:05 ValWood

I wonder if this. ticket could be processed. It's straightforward (it is part of my review of everything annotated to. "regulation of process".This isn't regulation, but the gene products annotated to it end up in the "regulation of ....." bin (and hence will be excluded from enrichment /slims)

ValWood avatar Sep 19 '22 17:09 ValWood

Hi @ValWood

It's not so straight forward because once we remove the regulation parents, this term has no more parents.

I wonder 'cohesin loading' and 'cohesin unloading' should not be deleted in favor of the corresponding MF: 'GO:0061775 cohesin loading activity' GO:0140670 ATP-dependent cohesin unloading activity (created in #21700)

Note that we would need to rehouse annotations to GO:1905343 regulation of cohesin unloading (3 SGD) and GO:0071922 regulation of cohesin loading (23 EXP)

pgaudet avatar Sep 20 '22 05:09 pgaudet

I considered that for a while, but cohesin loading and unloading are multistep processes:

Screenshot 2022-09-20 at 08 38 06

https://www.researchgate.net/publication/290392950_DNA_Entry_into_and_Exit_out_of_the_Cohesin_Ring_by_an_Interlocking_Gate_Mechanism/figures?lo=1

ValWood avatar Sep 20 '22 07:09 ValWood

Actually what you suggest would work. Pds5/Wpl would be described as a cohesin loader/unloader activity, and the other steps (like the ATPase which is intrinsic to the cohesin, and the acetylation. step would just be part of "cohesion". Otherwise what is "cohesion"?

ValWood avatar Sep 20 '22 07:09 ValWood

I have been trying to annotate this pathway since the Noctua workshop in Hinxton. I think it was about 10 years ago ;)

ValWood avatar Sep 20 '22 07:09 ValWood

Right - because although the steps can be decomposed, it seems like the overall activity of each complex is 'loading/loader' and unloading/unloader'

pgaudet avatar Sep 20 '22 07:09 pgaudet

Yes. I was being dim.

ValWood avatar Sep 20 '22 07:09 ValWood

Need to change the labels for the MFs -

  • GO:0061775 cohesin loading activity' -> cohesin loader activity'
  • GO:0140670 ATP-dependent cohesin unloading activity -> ATP-dependent cohesin unloader activity

pgaudet avatar Sep 21 '22 10:09 pgaudet

Yes I fully agree, cohesin loader (NIPB and SCC4) and unloader (WPL) are much better as MFs than BPs. The BP is sister chromatin cohesion (and is in fact restricted to S-G2/M phases) as in G1, there are no sister chromatids yet. In G1, S and G2/M chromosome looping is performed by cohesin.

colinlog avatar Sep 21 '22 12:09 colinlog

Hi Colin. Doesn't APL function as both a loader and an unloader. I am sure I have annotations to both?

ValWood avatar Sep 21 '22 12:09 ValWood

Ignore. I did . I don't seem to now...

ValWood avatar Sep 21 '22 12:09 ValWood

do we need "maintenance of mitotic sister chromatid cohesion" I was wondering if the term was applicable to sororin, so I looked at what's currently annotated to the term. There are 11 experimental annotations, it looks like a mix of things?

https://www.ebi.ac.uk/QuickGO/annotations?goUsage=descendants&goUsageRelationships=is_a,part_of,occurs_in&goId=GO:0034088&evidenceCode=ECO:0000269&evidenceCodeUsage=descendants

Antonialock avatar Sep 22 '22 09:09 Antonialock

There is loading(requiring the mis4/SSl3 loader) and then the loader isn't required for maintenance.

We were discussing whether there is a need for establishment and maintenance. I am not sure. The cohesin is loaded in telophase/ G1 (or is it throughout thee cell cycle?) , then it is 'established' during replication (behind the fork) and 'maintained until anaphase.

@colinlog may be best to advise which steps can be MF and where we need separate BP...

ValWood avatar Sep 22 '22 09:09 ValWood

To me sister chromatid cohesion is the BP. The MFs are establishment (loading cohesin ring) and dissolution (unloading cohesin ring). The ;maintenance is the integrity of the cohesin ring itself, I would say.

There are the specialised meitoic division aspects of cohesion of course.

There is the motor activity of the cohesin complex, which is a loop extrusion activity in the BP chromatin looping, as far as we know.

colinlog avatar Sep 22 '22 15:09 colinlog

@pgaudet remember to merge the "regulation of cohesion loading" into the "regulation of (mitotic?) cohesion"

ValWood avatar Sep 29 '22 17:09 ValWood

ping

ValWood avatar Nov 24 '22 14:11 ValWood

Hi @ValWood What is the action exactly? you write merge "regulation of cohesion loading" into the "regulation of (mitotic?) cohesion"

This term does not exist. We do have ' regulation of sister chromatid cohesion '; is that what you mean? We dont seem to have ' regulation of mitotis sister chromatid cohesion ' (see children of mitotic sister chromatid cohesion - it has no regulatory children https://www.ebi.ac.uk/QuickGO/term/GO:0007064), although we do have a very large number of terms in this branch:

image

Thanks, Pascale

pgaudet avatar Nov 28 '22 10:11 pgaudet

Since we are not doing merges anymore we should obsolete.

we (should) now have MF terms for cohesin loading and cohesin unloading so we can obsolete any terms in BP with loading or unloading.

when terms say "regulation of cohesin loading" the appropriate annotation would be "regulation of cohesion". So regulation of mitotic sister chromatid cohesion loading for example would be "regulation of mitotic sister chromatid cohesion"

You are correct, there are too many terms, I think these might be best dealt with by a comprehensive annotation review of the pathway. There are different paths operating at the arms and the centromeres but we don't need all of the establishment and maintenance terms.

I think things will be clearer once the loading and unloading terms have gone.

ValWood avatar Nov 28 '22 10:11 ValWood

Just to make sure we're on the same page: The MFs do exist:

GO:0061775 cohesin loader activity

GO:0140670 cohesin unloader activity

pgaudet avatar Nov 28 '22 12:11 pgaudet