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

8/13/2019 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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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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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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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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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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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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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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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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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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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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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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Blok 4 - IT 2 - Siklus Dan Pembelahan Sel - SNA

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