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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 SA Cyclin 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 pe Control 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 mammals Focus 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 cyl Last stages of mitosis regulated by phosphatases + Nudlear envelopes are brought back by

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