The Cell Cycle and Its
+ Many rounds are needed:
‘Tomake a new organism
*Toreplace cells lost by
wear and tea
Main events:
Duplication of DNA
“Sogregation of chromosome
(also called chromosome cycle)
Regulation So ly
=o :
ony =
—————
Cell division cycle sor) -co
Signal for the proliferative cycle
‘The tanston atthe restrcton point (R) or start
(S) pont n G, commits the ce tothe
Proliferative cycle
"the condtions that signal this transition are
‘ot present, the cell exits the cell cycle and
‘enters Gp, a nonprolferative phase during
which growth, diferentation and. apoptosis,
Categories of cells
+ Calis tat no lnger divide ar they ditoronite
‘ore cas)
* Cols hat nemally dont dive but canbe
[raucoa es etnae w proper shasus We el
Fimpoves)
«nt tet et ty
Sa mane
pope tet
=Initial Studies on the cell cycle
+ Cel fusion experiments- Puto Rao and
Robert Jchasen Univ of Colorado
~Gt and 5 phase calls
= G2and M cols
Malls and S phase cets
= G2and S phase cols
Results suggest regulation inthe entry to
‘the diferent stages
ee
Cycn-ccomplesreguates/controtsenty into diferent
sagen the cycle
—tsnonslegss ums Jeol old
Focus on cyclin: Lessons from sea
urchin eggs
+ Cycin was fe oad from se8 urchin oops
+ When other coeyestcats were montored for
‘existance ofthe same protin, yen was fund o be
present nll eukaryote ella
Cyclin Regulates Mitosis/Maturation Promoting
Factor (MPF) Activity
No MPF actuty was observed without protein
synthesis
-certain proteins not synthesized all the
time but oscilate withthe cel eye; hese
proteins were lle called cycin
sien cols were treated wt RNAse, cycle
Was arrested: addon of cyein mRNA
rescued ffm acest
-when cycin level reaches a threshold tis
partly responsible fer actvating MPF
SACyclin regulates MPF activity
(cont'd)
+ Oyen locales ein ak compl inthe nucleus
+ Ojoinis ogres o ont Mone
Dearne by ubgutatin
Det rated ycin hat can at bat ot
opm proved the eo ein nd
sory pes of yn the main tte esis
{yen ein commts oa eter phase
Focus on cyctin dependent kinase
(Cdk) Lessons trom mutant yeast
+ cyclin dependent kinases (cdk) -
catalytic subunit of MPF and SPF
+ Cdkwas frst observed in mutant yeast and
called ede (cel division cycle)
Mutant yeast without ede failed to enter
riosis, ust kept elongating
~Mutant yeast with over expressed ede entered
Mpeematurey
+ cdc in yeast lead to ciscovery of eck genes in
+ Cak was observed to bea phosphoryiating unt
Lessons from mutant yeast (cont'd)
‘ther eukaryote calls, gone i highly
‘conserved can replace one win te other
‘cross species
buteant phosphorylate without a parner,
cycin:n yeast ts partners ede13 equivalent
to oye).
(Cdc2-cde13 of yeas is equivalent to Xenopus
peControl of cdk activity
‘eDecuced sequences and biochemical studies
found that he folowing proteins regulate cdc 2
‘actvy, but only when eyein is bound to cdc?
wood inhitory
Phosphorylation at yr 16 and Thr 14
10425 phosphatase activator, removes
‘Phosphate om Tyr iSactvatr ahonase
scAK eae? activating Kinase)
Dhospherylte at activating Thr 161
soo micedu/ane repel ett nt
crac
‘The Nobel Pie wanes ia Psa a Medcn 20 fr
More Focus on MPF
+ Mace up of eycin dependent kinase (cde)
‘and mote oyein
+ Cycin dependent kinase phosphorites
‘roeins in serine and threonine residues
+ Auniversal feature in col cycle of eukaryotic
els rom yeast to mammalsFocus on MPF activity (cont'd)
+ ‘Start of acy is autocataltc (dependent on level
cof cytn)
+ Cdk of MPF phosphorites
= Nuclear lamins- breakdown of nuclear envelope
contancins-condense DNA
Cdk of MPF phosphorylates (cont'd)
~ Centresomes- production of spindle fers
Directly o ndrecty phosphorylates other
proteins
Focus on MPF
+ These events take the cell to metaphase
of mitosis,
+ Atthis point, the M-phase promoting factor
activates the anaphase-promoting
‘complex (APCIC)
MPF activates Anaphase Promoting
‘ComplexiCyclosome (APCIC)
‘APCs prod M phase to continue
Targets anaphase inhibitor (SMC proteins) for
ubiquitination hence proteasome degradaton
Upon destruction of cohesins/securin-
daughter chromatids. separate towards
the poles |
Other Roles of APC
“destroys cyclin B at late stage to maintain
Sender sate com tt oer
‘segregation) by aiaching ito ubiquitin targeting
ior destruction by proteasomes
“tums on synthesis of G,cycin forthe next tun
ofthe cylLast stages of mitosis regulated by
phosphatases
+ Nudlear envelopes are brought back by