wiki:ChromosomeSegregation

Version 207 (modified by vw253, 6 years ago) (diff)

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Annotation Priorities

  • Processes relevant to the most , (especially anything related to cell cycle regulation, cancer, broadly conserved)
  • Have large percentage of functionally characterised genes (for example mitochondrion organization has 40 published genes/294, so is low priority compared to cytokinesis 136/139)
  • Are mature enough to be able to construct pathways/networks
  • New gene characterizations -These should be sent out for community curation, but followed up
  • phenotype screens see canto
  • Process priorities : chromosome segregation, DNA metabolism, cytokinesis, regulation of mitotic cell cycle, any signaling pathway, chromatin organization, , cytokinesis, establishment or maintenance of cell polarity, protein modification by small protein conjugation or removal
  • kinases, phosphatases, GTPAses, ubiquitin ligases, protein methylases (anything with direct substrate to improve networks)

HIGHEST priority genes/complexes/papers

mus81 PMID:15805465 Mus81-T239A disrupts the ability of Cds1 to bind and phosphorylate Mus81 and causes hyper-recombination upon hydroxyurea-induced replication arrest
cdc2PMID:8557037mcs6 substrate cdc2
cdc2PMID:6526270uniprot has this paper for allele cdc2-4w C67F (we have 'unspecified')
Clp1PMID:18378776 Clp1 in turn dephosphorylates the essential F-BAR scaffold protein Cdc15, CR assembly
plo1?????mid1? is a substrate
Sid2Chen et al. 2008phosphorylates the nonessential Cdc14 phosphatase Clp1 to foster Clp1’s cytoplasmic retention
Mre1 complexPMID:21008122 and papers cited within In humans and both yeasts, DSBs are initially detected and processed by the 1Xrs2 (MRN) nucleolytic protein complex in association with the Tel1ATM checkpoint kinase and the Ctp1CtIP/Sae2 DNA-end processing factor;...implies tel1 /rad50/nbs1 should be annotated to GO:0000729 The functions of ATM and ATR orthologs are intimately tied to the detection and nucleolytic processing of DSBs. ATMTel1 localizes at DSBs by interacting with (MRN) protein complex, which directly binds DNA ends (12, 20, 24, 50, 52). use these papers to annotate the missing connection between tel1 and the mre11 complex
crb2PMID:14739927 Finally, we show direct interaction between Rad3 and Crb2, which is inhibitory to Rad3 activity (direct enzyme regulator substrate)
crb2PMID:21098122 There are two pathways that lead to Crb2 localization at sites of DNA damage (10). One pathway requires two inde- pendent histone modifications: (i) phosphorylation of the C- terminal tail of histone H2A
Tel1 PMID:21098122 Tel1 phosphorylation of histone H2A at DSBs depends on its interaction with the Nbs1 subunit of MRN complex (52). (add tel1 targets as histones)
crb2 ????Find physical interaction with Rad9
All histones????These are often not annotated with their roles in cell cycle regulation and repair, and so they are excluded from the graphs (also need to have specific nucleosome terms, 'what do you call a normal nucleosome?l' and 'centromere specific'
srw1PMID:9571240, PMID:9736616 PMID:10921878 has no mitotic cell cycle regulation annotation
fnx1 & 2PMID: 18503766 This wouldn't normally be a priority, but I'm putting it in becasue the exisitng transport GO annotations look a bit of a mess (stretch) ... need to get detailed phenotypes and then decide what it is possible to infer sensibly
Scf complex?????-
scp1???Skp1 doesn't have ubiquitin ligase activity so these MF annotations should probably be on BP
dsc2???activation of sre2 TF? positive regulation of SREBP signaling pathway by transcription factor cleavage? for the Dsc subunits? may be in one of the other dsc papers.... chung paper?
cul1?????-
ppa1?????targets ppe1?
ppe1?????targets pim1?
pck1?????targets ppe1?
pck1?????phosphorylates mcm2,4,6, caf1, swi6,rad9, swi3, mrc1 crm1 and other importins
Pad1/Rpn11 and Mts3/Rpn12 are subunits of the lid subcomplex????? in PMID: 16149916 Mutations in the genes encoding these two subunits were isolated in a screen for mutants that were both esistant to methyl 2-benzimidazolecarbamate, a microtubule in- hibitor, and Ts for cell-cycle progression [19,20]. Ts mutations in both genes cause arrest of the cells in mitosis, probably because of a failure to degrade cyclin B/Cdc13 and securin/Cut2.
mde4 ????? Previous results showed that in interphase, when Mde4 is dephosphorylated, the Mde4-Pcs1 complex localizes to the nucleolus and to the kinetochores, which cluster at the nuclear periphery next to the spindle pole bodies (SPBs) [6,8]. As cells enter mitosis and Mde4 becomes phosphorylated, Mde4- Pcs1 leave the nucleolus but remain at the kinetochores [6,8]. PubMed?: 17627824/12689592]
cdc20 ????? When Cdc20 is overexpressed, securin can be degraded during interphase, whereas other destruction box proteins will remain stable. In cells lacking Cdc20, securin remains stable, and sister chromatids will not separate (Visintin et al., 1997).
cut7|????? In the temperature-sensitive cut7 mutant, spindle formation is blocked shortly after duplication of the SPB. The mitotic spindle radiating from the opposite poles cannot interdigitate and thus remains as a V shape (Hagan and Yanagida, 1992). The cut7- specific defect generates a condition whereby the bipolar attachment of the spindle to kinetochores is not achieved. Previously, we demonstrated that this defect causes an arrest in a mad2+-dependent manner (Kim et al., 1998). At the restrictive temperature the majority of Mad2-GFP was found on condensed chromosomes as one or more speckles (Fig. 4).

Process priorities

Chromosome segregation (Val, but feel free to do any genes or complexes that I haven't started)

process chromosome segregation: genes 207 of which 183 published esyN
gene/complexstatus date
fta1 Mis6-Sim4 complex annotation complete6/1/2015
fta2 Mis6-Sim4 complex annotation complete 6/1/2015
fta3 Mis6-Sim4 complex annotation complete 6/1/2015
fta4 Mis6-Sim4 complex annotation complete 15/1/2015
fta6 Mis6-Sim4 complex annotation complete 15/1/2015
fta7 Mis6-Sim4 complex annotation complete except CC PMID: 2478970820/1/2015
mis6 Mis6-Sim4 complex annotation complete except CC PMID:24789708 PMID2537524020/1/2015
mis15 Mis6-Sim4 complex annotation complete 6/1/2015
mal2 Mis6-Sim4 complex PMID: 12242294 + others -
sim4 Mis6-Sim4 complex annotation complete 20/1/2015
sos7 NMS complex annotation complete 6/1/2014
spc25 NMS complex/ Ndc80 complexannotation complete needs annotation to ndc80 complex20/1/2015
spc7 NMS complex in progress IS THIS TURNING SAC SIGNALLING OFF? PMID: 17035632-
ndc80 NMS complex/Ndc80 annotation complete needs annotation to ndc80 complex -
mis12 NMS complexto do PMID:15930132 check biorientation ann-
mis13 NMS complexannotation complete 20/1/2015
mis14 NMS complexannotation complete 6/1/2014
nnf1 NMS complex to do PMID:17035632 -
mis16 CENP-A recruiting complex complete except CC PMID:22771823 and scm3* papers-
mis18 CENP-A recruiting complex complete except CC PMID:24789708 15/1/2015
mis19 CENP-A recruiting complex complete except CC PMID:25375240 15/1/2015
mis20 CENP-A recruiting complex annotation complete 20/1/2015
nuf2 Ndc80 complex 2 plus PMID:23770679 (out for CC) needs annotation to ndc80 complex-
spc24 Ndc80 complex annotation complete needs annotation to ndc80 complex20/1/2015
dad1 DASH complex to do PMID:16079914 PMID:16079915 -
csm1 monopolin complex in progress PMID: 20935472 PMID:12689592 plus…-
mde4 monopolin complex TODO ONLY PMID:19523829 PMID:20723757 PMID: 22264609-
mis17 annotation complete 6/1/2015
cnp20 annotation complete 6/1/2015
dis1 PMID:16920624 plus… -
ppe1 to do PMID: 12773390 -|
scm3 to do PMID: 19217403 PMID: 19217404 (also mis16)-
cnp1 in progress-
mal3 in progress-
dad1 PMID:17352737 -
cnp3PMID:15791413 PMID: 24449889 autonomous-
sds22 phoshatase PMID: 1846086 PMID: 15335873 PMID: 8374168 -
cnd1 condensin complex non-SMC subunit PMID: 18362178-
cnd2 condensin complex non-SMC subunit PMID:21633354-
cnd3 condensin complex non-SMC subunit --
hos2 PMID:17352737 plus -
pcs1PMID:20935472 plus... -
ams12chen et al, cenp-a loading -
nsk1abnormal clustering of kinetochores to spindle pole bodies-
cut4/apc1 anaphase-promoting complex subunit, platform subcomplex ???-
apc4/cut5 anaphase-promoting complex subunit, platform subcomplex ???-
apc5/cut5 anaphase-promoting complex subunit, platform subcomplex TPR ???-
apc15 anaphase-promoting complex subunit, platform subcomplex ???-
apc8 anaphase-promoting complex TPR lobe subcomplex ???-
cut9/apc6 anaphase-promoting complex TPR lobe subcomplex ???-
apc3 anaphase-promoting complex TPR lobe subcomplex ???-
apc12 anaphase-promoting complex subunit TPR lobe accessory factor Hcn1???-
apc13 anaphase-promoting complex subunit TPR lobe accessory factorPMID: 15060174 only-
apc10 anaphase-promoting complex substrate recognition subunit Apc10PMID: 9736616 PMID: 10526233 PMID: 12653962 only-
apc2 anaphase-promoting complex cullin family subunitannotation complete24/4/2015
apc11 anaphase-promoting complex ubiquitin protein-ligase E3 subunit annotation complete24/4/2015
apc14 anaphase-promoting complex (might be apc16 ortholog)annotation complete24/4/2015
alp4 gamma tubulin complex Spc97/GCP2 subunit Alp4PMID:18418055 16611237/8 15772152 CC-PMID: 24704079 PMID: 23886939-
alp6 gamma tubulin complex Alp6PMID: 23886939 PMID: 24704079-
alp16 gamma tubulin complex Alp16annotation complete 23/4/2015
gfh1 gamma tubulin complex Gfh1PMID:15004232 only-
gtb1 gamma tubulin Gtb1PMID: 15280226 only -
mod21 gamma tubulin complex Mod21PMID:17021256 only-
mzt1 mitotic spindle organizing protein Mzt1 annotation complete23/4/2015
mad2 & SCC mad2 targets slp1 acting as a mitotic anaphase-promoting complex inhibitor activity---

other chromosome segregation

dis2 phosphatase (PMID:14765108 - describes checkpoint termination Dis2 abrogates Chk1 phosphorylation and activation in vivo, ) PMID:2245912 PMID:8389306 PMID:8305731 PMID:7983142 PMID:7957097 PMID:9264466 PMID:9790575 PMID:10668632 PMID:11085271 PMID:16411888 PMID:17895368 PMID:19592249 PMID:21664573 (Out for CC PMID:21703453 PMID:21965289 PMID:23333317) (Iain Hagan PMID:25487150) -
dis1 XMAP215/ TOG/Stu2-family homolog, binds microtubules and localizes to kinetochores (Nakaseko et al., 2001). Mutants in dis1 lack the chromosome alignment phase in metaphase and arrest with elongated spindles and segregated but unseparated chromosome pairs (Nabe- shima et al., 1998; Ohkura et al., 1988).dis1 mutants arrest with an activated spindle checkpoint and appear to ex- perience an increase in sister chromatid cosegregation (70%) at full restrictive temperature. Such cosegregation results when mono-oriented attachment of sister kineto- chores to microtubules from the same SPB is not corrected. Since dis1 mutants lack the phase of constant spindle length when chromosomes are properly aligned

Notes and annotation questions on chromosome segregation

  • read review PMID: 23512483
  • is CENP-A containing nucleosome assembly part of kinetochore assembly? Although the outer repeats play an important role in sister centromere cohesion and possibly help to properly orient the multiple kinetochore microtubule attachment sites (Pidoux and Allshire, 2004
  • Centromeres: getting a grip of chromosomes. Curr. Opin. Cell Biol. 12, 308–319., the central region is needed for the assembly of the kinetochore per se and the interaction with the mitotic spindle fibers
  • what is the relationship between kinetochoe assembly, spindle elongation and chromosome segregation (currently disjoint)
  • reannotate ndc80 and MIND subcomplexes annotate PAS complex
  • ask expert to look at CENP_A assembly vs CENP-A assembly phenotype
  • no substrates currently annotated for APC, look for motifs ABBA, KENm D-Box, C-BOX, F-box, 2BR, LRRL
    • I think from humanUbc11 is the APC E2, has some substrates assigned (cdc13 direct, slp1 indirect), but sc imlies ubc4 and ubc1 (amybe all)
  • possible substrates to annotate mitotic securin and cylin; late mitosis cdh1 , cytokinesis aurora, cyclins, cdc29; G1 geminin, cdc6, skp2,ubcH10(ubc11)
  • check all know APC targets annotated

Cytokinesis but feel free to do any genes or complexes that I haven't started

process cytokinesis: 139 of which 136 published esyN
gene/complexstatus date
lsk1 in progress-
mac1 annotation complete 22/1/2014
lkh1 chained 12565823 -

Notes and annotation questions on cytokinesis

  • previously considered to be linear assembly mid1- rng2- others. But if you can ectopically localize rng2 you can get all of the others (any one of the 3 will work)

check should mid1 be ring assemlby or localization only?

check mid1 NOT assembly? positioning
main target of mid1 is rng2 rng3- myosin specific chaperone add to wiki with mohan paper details

Regulation of mitotic cell cycle

process regulation of mitotic cell cycle: l genes 258 of which 231 published esyN
gene/complexstatus date
psk1 annotation complete (except PMID: 22976295 out for CC) 16/2/2015

Notes and annotation questions on cell cycle regulation

  • Only include gene products here not covered in chromosome segregation, cytokinesis or DNA metabolism
  • genes which should be annotated to "signalling" based on the signalling components of the cell cycle regulation network
  • Need to do cytokinesis checkpoint, G1 cell size control checkpoint, DNA damage checkpoint (ask experts to check specific checkpoint lists)
Misc other annotation complete
gene/complexstatus date
mcp60 annotation complete 16/2/2015