Blok 4 - IT 2 - Siklus Dan Pembelahan Sel - SNA

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    Cell cycle is the fundamentalmeans by which all living

    things are propagatedCell division

    Cell growth

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    Cell cycle:Have a control system

    There are extracellularsignals act on thecontrol system toregulate cell division ina multicellularorganism

    The majority of cells also:double their massduplicate all their

    cytoplasmicorganelles in eachcell cycle

    The duration of the cell cycle: Varies greatly from one cell type to another

    Fly embryos have the shortest : 8 minutesMammalian liver cell can last longer than a year

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    Pembelahan Sel bertujuan untuk :

    Reproduksi individu baruProliferasi

    Pertumbuhan & perkembangan (dari

    sel telur terfertilisasi)Menggantikan sel yang rusakMenggantikan sel yang masuk keprogram kematian sel

    MitosisMeiosis

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    20 m200 m

    (b) Growth and development.This micrograph shows asand dollar embryo shortlyafter the fertilized egg divided,forming two cells (LM).

    (c) Tissue renewal. These dividingbone marrow cells (arrow) willgive rise to new blood cells (LM).

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    Semua organisme kompleks

    berasal dari a single fertilizedegg.

    Melalui pembelahan sel, jumlah sel meningkat

    Sel kemudian terspesialisasidan berubah menjadifungsinya masing2

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    Tipe pembelahan sel

    Mitosis:Growth, development & repairAsexual reproduction (yields identical cells)Occurs in somatic (body) cells

    Meiosis:Sexual reproduction (yields different cells)Occurs in specific reproductive cells

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    Siklus PembelahanSel, secara umum

    membutuhkan :1. Replication DNA : to produce a pair of

    genetically identical daughter cells2. Replicated chromosomes must be segregated into

    two separated cells

    Pembelahan sel mendistribusikan satu setkhromosom identik ke sel anak

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    Cell cycle several distinct phases:

    Mitosis, the process of nuclear divisionInterphase, longer period that elapsesbetween one M phase & the next

    Fase Mitosis :Profase, Prometafase, Metafase,

    Anafase & Telofase

    Fase Interfase :G1, S & G2

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    Fase-fase dalam siklus sel

    Siklus sel terdiri dari

    Fase mitosisInterphase

    INTERPHASE

    G1 S(DNA synthesis)

    G2

    Interphase G1 phase S phase G2 phase

    The mitotic phase mitosis cytokinesis

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    Cell Cycle: Mitosis phase

    In mitosis: The nuclear envelope breaks down The contents of the nucleus condense into visiblechromosomes

    The cells microtubules reorganize to form themitotic spindle that will eventually separate thechromosomes

    As mitosis proceeds, the cell seems to pausebriefly in a state called metaphase

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    Cell Cycle: Mitosis phase

    Metaphase : The chromosomes already duplicated are alignedon the mitotic spindle, poised for segregation

    The separation the duplicated chromosomesmarks the beginning of anaphase Anaphase : The chromosomes move to the poles of thespindle, where they decondense & re-form intactnuclei

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    Mitosis terdiri dari 5 phasesProphasePrometaphase

    G2 OF INTERPHASE PROPHASE PROMETAPHASE

    Chromatin(duplicated)

    Early mitoticspindle

    Aster

    CentromereFragmentsof nuclearenvelope

    Kinetochore

    Nucleolus Nuclearenvelope

    Plasmamembrane

    Chromosome, consistingof two sister chromatids

    Kinetochore

    microtubule

    Cen trosomes(with centriole pairs)

    Nonkinetochoremicrotubules

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    Metaphase Anaphase Telophase

    Centrosome atone spindle pole

    Daughter

    chromosomes

    METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

    Spindle

    Metaphaseplate Nucleolus

    forming

    Cleavagefurrow

    Nuclearenvelopeforming

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    Mitosis in a plant cell

    1 Prophase.The chromatinis condensing.The nucleolus isbeginning todisappear.Although notyet visiblein the micrograph,the mitotic spindle isstaring to from.

    Prometaphase.We now see discretechromosomes; eachconsists of twoidentical sisterchromatids. Laterin prometaphase, thenuclear envelop willfragment.

    Metaphase. Thespindle is complete,and the chromosomes,

    attached to microtubulesat their kinetochores,are all at the metaphaseplate.

    Anaphase. Thechromatids of eachchromosome haveseparated, and thedaughter chromosomesare moving to the endsof cell as theirkinetochoremicrotubles shorten.

    Telophase. Daughternuclei are forming.Meanwhile, cytokinesishas started: The cellplate, which willdivided the cytoplasmin two, is growingtoward the perimeter of the parent cell.

    2 3 4 5

    NucleusNucleolus

    ChromosomeChromatinecondensing

    Figure 12.10

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    Cell Cycle: Mitosis phase

    The cell is then pinched in two by a processcalled :Cytokinesis which is traditionally viewed as theend of the mitosis phase or M phase of the cellcycleIn most cells the whole of M phase takes only

    about an hour, which is only a small fraction ofthe total cycle time

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    Cytokinesis

    Sel hewan : kerutan bidang pembelahan cincin kontraktil dari mikrofilamenSel tumbuhan : pembentukan cell plateoleh

    vesicle Hasil : 2 sel anak yang identik dengan selinduk

    Mitosis pada eukaryot serupa binary fissionpadabakteri

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    Origin ofreplication

    Cell wall

    Plasmamembrane

    Bacterialchromosome

    E. coli cell

    Two copiesof origin

    Chromosome

    replication begins.Soon thereafter,one copy of the originmoves rapidly towardthe other end of thecell .

    Replication continues.One copy of the originis now at each end ofthe cell.

    Origin Origin

    Replication finishes.The plasma membranegrows inward, andnew cell wall isdeposited .

    Two daughtercells result.

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    Cell Cycle: Interphase

    Interphase :Under the microscope this appears, as anuneventful interlude in which the cell simply growin size.

    But other techniques, interphase is actually a busytime for the proliferating cell, which elaboratepreparations for cell division

    In particular, the DNA in the nucleus is replicated

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    Cell Cycle: Interphase

    Replication of the nuclear DNA occurs during aspesific part of interphase called: The S Phase of the cell cycle (S = synthesis)

    The interval between the completion of mitosis &the beginning of DNA synthesis is called :

    The G 1 phase

    The interval between the end of DNA synthesis &the beginning of mitosis is called:

    The G 2 phase

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    Cell Cycle: Interphase

    G1 & G2 provideadditional time forgrowth:

    If interphase lastedonly long enough forDNA replication, the

    cell would not havetime to double itsmass before it divided

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    Cell Cycle: Interphase

    During G 1 The cell monitors itsenvironment & itsown size & when thetime is ripe, takes adecisive step thatcommit its to DNAreplication &completion of adivision cycle

    The G2 phaseprovides :a safety gap, allowingthe cell to ensure thatDNA replication iscomplete before itplunges into mitosis

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    Cell Cycle: Interphase

    Cells in G1 :If they have not committed themselves toDNA replication, can pause in their progressaround the cycles and enter a specializedresting state, often called :G0 ( G zero), where they can remain for days,

    weeks or even years before resumingproliferation

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    Cell Cycle: Interphase

    Because cells require time to grow beforethey divide, the standard cell cycle isgenerally 12 hours or more in a mammal

    tissues Although the lengths of all phases of thecycle are variable, by far the greatest

    variation, in most of the commonly studiedtypes of cells occurs:

    In the duration of G1

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    Central Control System

    1. in G1, just before entry into S phase2. in G2, at the entry to mitosisIn higher eucaryotic cells signals that arrest thecycle usually act at:

    the G 1 control point This checkpoint is called start in yeastIn mammalian cells the G 1 checkpoint

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    Pengaturan siklus

    sel : pengaruhinternal daneksternal

    Sel-sel cancerterjadi karenakeluar darikontrol siklus sel

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    Central Control System

    In a continuously cycling cell :the G 1 checkpoint is the point wherethe cell cycle control system triggers aprocess that will initiate S phase

    The G 2 checkpoint is where it triggers aprocess that will initiate M phase

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    Protein Kinase based Machine

    The cell cycle control system is based on twokey families of protein

    1. The family of cyclin dependent protein kinases (=

    Cdk), which induce downstream processes byphosphorylating selected proteins on serines &threonines

    2. A family of specialized activating proteins, called

    cyclins, that bind to Cdk molecules & control theirability to phosphorylate appropriate target proteins

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    Protein Kinase based Machine

    There are two main classes of cyclins: 1. Mitotic cyclins, which bind to Cdk

    molecules during G2 & are required forentry into mitosis2. G1 cyclins, which bind to Cdk molecules

    during G1 & are required for entry into S

    phase

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    Protein Kinase based Machine

    The events that drive the cell into mitosis are asfollows:

    Mitotic cyclin accumulates gradually during G2 &bind to Cdk to form a complex known as M-phasepromoting factor (MPF)

    This complex is at first inactive, but through

    the action of other enzymes that phosphorylate &dephosphorylate it, it is converted to an active form

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    Protein Kinase based Machine

    Kemudian MPF aktif yang berlebihanmentrigger downstream untuk

    menggerakan sel memasuki mitosisMPF di-inaktif-kan secara tiba-tiba secaraequal melalui degradasi siklin mitosis pada

    batas metafase-anafase, yangmemungkinkan sel keluar dari mitosis

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    Akumulasi protein terjadi secara continu tiap interfasesampai transisi antara metafase ke anafase dan

    kemudian secara tiba-tiba luruh (periodik)Berdasarkan pola demikian, protein cyclinMPF aktif, jika cyclin mencapai [ambang] & MPFinaktif, jika cyclin terdekstruksi (siklus keluar dari fase

    mitosis)

    Aktivasi&

    Inaktivasi

    MPF

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    Hipotesis : aktivasi MPF secara normalditrigger segera begitu [cyclin] mencapainilai ambang

    Waktu pengaktifan MPF tidak ditentukansecara eksklusif oleh cyclin tetapi

    tergantung pada regulasi subunit Cdkdengan protein lain

    Aktivasi & Inaktivasi MPF

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    Degradasi cyclin mentrigger keluar dariM-phaseSecara normal, cyclin secara tiba-tibadilisiskan proteolisis antara metafase-anafaseProses ini butuh signal pada rantaipolipeptida cyclin (by providing a site forattachment for ubiquitin) sehingga menjaditarget untuk didegradasi proteasome

    Aktivasi & Inaktivasi MPF

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    FEEDBACK CONTROL

    Jika sel digerakkan mitosis, sebelum replikasiDNA selesai :

    Incomplete sets of chromosome to its daughters

    Jika sel membelah sebelum chromosomemitotic spindle:

    Alokasi kromosom not equalantara sel anak

    Feedback control menunda mitosis sampaireplikasi DNA komplet

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    FEEDBACK CONTROL

    Feedback control depend on inhibitory signalfrom:

    unreplicated DNAunattached chromosome

    Feedback signals from incomplete replicated ordamage DNA that prevent the control system

    from passing the next checpoint untilreplication is complete or the damage isrepaired

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    Damage DNA generates a signal to delay Mitosis : feedback control operates at mitotic entry checkpoint to prevent damage DNA from

    entering mitosis until the damage is repairedProtein p53 (sel mammalia) terakumulasi saat ada kerusakan DNA,sistem tertahan di G 1 menahan sel masuk ke fase S dengan DNAyang rusak

    FEEDBACK CONTROL

    Feedback control mechanism : cellshalt in S phase

    Caffeine menginaktifkan mekanismefeedback control

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    Cell Cycle in Multicellular Organism

    Multiple cyclin :Cyclins A, B, C, D, E, &F

    Cdc2 ~cyclin B : inducemitosisCdk2 ~ cyclin E : inducepassage past G1 checkpointCdk2 ~ cyclin A : toactivate the DNAreplication machinery

    standard vertebrate cell cycle

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    Cell Cycle in Multicellular Organism

    Cell growth & cell divisiondapat diregulasi secaraterpisah penting bagiorganisme multiseluler

    Beberapa faktor membuatsel tumbuh tetapi tidakdapat melewati G1 checkpoint & sebaliknya

    Sel neuron (G0 ) dapattumbuh tanpa pernahmembelah

    Sel neuron dan sel otot :do not divide at allSel liver secara normalmembelah satu atau duakali setiap tahunSel-sel epitel ususmembelah lebih dari 2 x

    sehariSel membelah tergantungkeadaan (eksternal &internal)

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    Tumor-supressor gene menghambat pembentukan dan

    pengaktifan sistem kontrol siklus selProto-oncogen kebalikan tumor-suppressor geneUnrestrained proliferation hasil mutasi yang meng-inaktif-kankedua kopi tumor-suppressor gene atau membuat satu kopi dari

    proto-oncogene menjadi hiperaktif

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    Cell Cycle inMulticellular Organism

    GF receptors activateintracellular phosphorylationcascade change geneexpression

    Gen yang diinduksi oleh GF :Early response gene (myc,fos, jun proto-oncogene)

    Delayed response gene(Cdk protein & several cyclin)

    requires products of theearly response gene

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    Cell Cycle: MulticellularOrganism

    Antiproliferation gene tumorsuppressor gene retinoblastoma (rb) geneLoss of this gene leads toexcessive cell proliferation in theimmature retina (cancer in theeye of children)

    Dephosphorylated Rb binds to& hold inactive gene regulatoryproteins

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    Cell Cycle: MulticellularOrganism

    Gene regulatory protein (such asmyc) : stimulate transcription oftarget genes cell proliferationPhosphorylated Rb, releasing thestimulatory proteins that activateproliferationIn normal cells the Rb protein ispermanently present (G 0 or

    cycling)G0: fosfat di dalam sel sedikit,menghalangi transkripsi

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    Hasilnya jumlah kromosom untukmasing-masing sel anak menjadisetengahnya

    Sel induk : diploid (2n) 4 sel anak

    haploid (n)

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    MEIOSIS

    Interfase :Replikasi kromosom/DNA selama S

    phase

    Fase meiosis I : mirip mitosis tetapi adamodifikasi pada fase profase, yi :

    Kromosom homolog berpasangan

    Chiasma crossing over rekombinasiFase meiosis II : tipikal pembelahan mitosis

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    Growing oocyte meiosis I (single round DNAreplication) meiosis II ( DNA replication)Grown Oocyte (meiosis I) is arrested : meioticprophase ( G 2 phase) just before entry into M phase

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    Fertilization releases the metaphase arrest egg

    completes its second meiotic division Then enters interphase of the first embryonic cellcycle

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    The standard cell cycle compared with the early

    embryonic cell cycle

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