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 Cell

cycle is the fundamental means by which all living things are propagated
Cell division Cell growth

The majority of cells also:

double

Cell cycle:
Have a control system There are extracellular signals act on the control system to regulate cell division in a multicellular organism

their mass duplicate all their cytoplasmic organelles in each cell cycle

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

Fly embryos have the shortest : 8 minutes Mammalian liver cell can last longer than a year
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Pembelahan Sel bertujuan untuk :

Reproduksi Proliferasi
Pertumbuhan

individu baru

& perkembangan (dari sel telur terfertilisasi) Menggantikan sel yang rusak Menggantikan sel yang masuk ke program kematian sel
Mitosis Meiosis
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200 m

20 m

(b) Growth and development. This micrograph shows a sand dollar embryo shortly after the fertilized egg divided, forming two cells (LM).

(c) Tissue renewal. These dividing bone marrow cells (arrow) will give rise to new blood cells (LM).

Semua organisme kompleks berasal dari a single fertilized egg. Melalui pembelahan sel, jumlah sel meningkat Sel kemudian terspesialisasi dan berubah menjadi fungsinya masing2

Tipe pembelahan sel

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

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

Siklus PembelahanSel, secara umum membutuhkan : 1. Replication DNA : to produce a pair of

2.

genetically identical daughter cells Replicated chromosomes must be segregated into two separated cells

Pembelahan sel mendistribusikan satu set khromosom identik ke sel anak

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Cell cycle several distinct phases:

Mitosis,

the process of nuclear division Interphase, longer period that elapses between 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 mitosis Interphase

INTERPHASE

G1

S (DNA synthesis)

Interphase G1 phase S phase G2 phase

G2

The mitotic phase

mitosis cytokinesis

Cell Cycle: Mitosis phase

In mitosis:
The nuclear envelope breaks down The contents of the nucleus condense into visible chromosomes The cells microtubules reorganize to form the mitotic spindle that will eventually separate the chromosomes

As mitosis proceeds, the cell seems to pause briefly in a state called metaphase
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Cell Cycle: Mitosis phase

Metaphase : The chromosomes already duplicated are aligned on the mitotic spindle, poised for segregation The separation the duplicated chromosomes marks the beginning of anaphase Anaphase : The chromosomes move to the poles of the spindle, where they decondense & re-form intact nuclei
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Mitosis terdiri dari 5 phases

Prophase Prometaphase

G2 OF INTERPHASE

PROPHASE

PROMETAPHASE

Centrosomes Chromatin (with centriole pairs) (duplicated)

Early mitotic spindle

Aster Centromere

Fragments of nuclear envelope

Kinetochore Nonkinetochore microtubules

Nucleolus

Nuclear Plasma envelope membrane

Chromosome, consisting of two sister chromatids

Kinetochore microtubule

Metaphase Anaphase Telophase

METAPHASE

ANAPHASE

TELOPHASE AND CYTOKINESIS

Metaphase plate

Cleavage furrow

Nucleolus forming

Spindle

Daughter Centrosome at one spindle pole chromosomes

Nuclear envelope forming

Mitosis in a plant cell

Chromatine Nucleolus condensing Chromosome

Nucleus

1 Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from.

2 Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelop will fragment.

Metaphase. The 4 spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate.

Anaphase. The 5 chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of cell as their kinetochore microtubles shorten.

Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell.

Figure 12.10

Cell Cycle: Mitosis phase

The cell is then pinched in two by a process called : Cytokinesis which is traditionally viewed as the end of the mitosis phase or M phase of the cell cycle In most cells the whole of M phase takes only about an hour, which is only a small fraction of the total cycle time
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Cytokinesis Sel hewan : kerutan bidang pembelahan cincin kontraktil dari mikrofilamen Sel tumbuhan : pembentukan cell plate oleh vesicle Hasil : 2 sel anak yang identik dengan sel induk Mitosis pada eukaryot serupa binary fission pada bakteri
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Origin of replication E. coli cell

Cell wall Plasma membrane Bacterial chromosome

Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Replication continues. One copy of the origin is now at each end of the cell.

Two copies of origin

Origin

Origin

Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result.

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Cell Cycle: Interphase

Interphase :
Under the microscope this appears, as an uneventful interlude in which the cell simply grow in size. But other techniques, interphase is actually a busy time for the proliferating cell, which elaborate preparations 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 a spesific 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 G1 phase

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

The G2 phase
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Cell Cycle: Interphase

G1 & G2 provide additional time for growth:

If

interphase lasted only long enough for DNA replication, the cell would not have time to double its mass before it divided
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Cell Cycle: Interphase

During G1
The

cell monitors its environment & its own size & when the time is ripe, takes a decisive step that commit its to DNA replication & completion of a division cycle

The G2 phase provides : a safety gap, allowing the cell to ensure that DNA replication is complete before it plunges into mitosis

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Cell Cycle: Interphase

Cells in G1 : If they have not committed themselves to DNA replication, can pause in their progress around the cycles and enter a specialized resting state, often called : G0 ( G zero), where they can remain for days, weeks or even years before resuming proliferation
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Cell Cycle: Interphase

Because cells require time to grow before they divide, the standard cell cycle is generally 12 hours or more in a mammal tissues Although the lengths of all phases of the cycle are variable, by far the greatest variation, in most of the commonly studied types of cells occurs: In the duration of G1
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Central Control System

1. in G1, just before entry into S phase 2. in G2, at the entry to mitosis In higher eucaryotic cells signals that arrest the cycle usually act at: the G1 control point This checkpoint is called start in yeast In mammalian cells the G1 checkpoint

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Pengaturan siklus sel : pengaruh internal dan eksternal Sel-sel cancer terjadi karena keluar dari kontrol siklus sel

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Central Control System

In a continuously cycling cell :

the

G1 checkpoint is the point where the cell cycle control system triggers a process that will initiate S phase The G2 checkpoint is where it triggers a process that will initiate M phase

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Protein Kinase based Machine

The cell cycle control system is based on two key families of protein
1.

2.

The family of cyclin dependent protein kinases (= Cdk), which induce downstream processes by phosphorylating selected proteins on serines & threonines A family of specialized activating proteins, called cyclins, that bind to Cdk molecules & control their ability to phosphorylate appropriate target proteins

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Protein Kinase based Machine

1.

There are two main classes of cyclins:

Mitotic cyclins, which bind to Cdk molecules during G2 & are required for entry into mitosis G1 cyclins, which bind to Cdk molecules during G1 & are required for entry into S phase

2.

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Protein Kinase based Machine

The events that drive the cell into mitosis are as follows:
Mitotic cyclin accumulates gradually during G2 & bind to Cdk to form a complex known as M-phase promoting 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 berlebihan mentrigger downstream untuk menggerakan sel memasuki mitosis MPF di-inaktif-kan secara tiba-tiba secara equal melalui degradasi siklin mitosis pada batas metafase-anafase, yang memungkinkan sel keluar dari mitosis

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Aktivasi & Inaktivasi MPF

Akumulasi protein terjadi secara continu tiap interfase sampai transisi antara metafase ke anafase dan kemudian secara tiba-tiba luruh (periodik) Berdasarkan pola demikian, protein cyclin MPF aktif, jika cyclin mencapai [ambang] & MPF inaktif, jika cyclin terdekstruksi (siklus keluar dari fase mitosis)

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Aktivasi & Inaktivasi MPF

Hipotesis : aktivasi MPF secara normal ditrigger segera begitu [cyclin] mencapai nilai ambang Waktu pengaktifan MPF tidak ditentukan secara eksklusif oleh cyclin tetapi tergantung pada regulasi subunit Cdk dengan protein lain

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Aktivasi & Inaktivasi MPF

Fosforilasi pada MPF (kompleks Cdc2-cyclin) ini masih inaktif jika residu tyrosine masih difosforilasi (inhibitory tyrosine phosphate) Inhibitory tyrosine phosphate harus di-remove untuk mengaktifkan MPF dikatalisis o protein Cdc25 (protein phosphatase)

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Aktivasi & Inaktivasi MPF

Degradasi cyclin mentrigger keluar dari M-phase Secara normal, cyclin secara tiba-tiba dilisiskan proteolisis antara metafaseanafase Proses ini butuh signal pada rantai polipeptida cyclin (by providing a site for attachment for ubiquitin) sehingga menjadi target untuk didegradasi proteasome

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FEEDBACK CONTROL

Jika sel digerakkan mitosis, sebelum replikasi DNA selesai :

Incomplete sets of chromosome to its daughters

Jika sel membelah sebelum chromosome mitotic spindle:

Alokasi kromosom not equal antara sel anak

Feedback control menunda mitosis sampai replikasi DNA komplet

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FEEDBACK CONTROL

Feedback control depend on inhibitory signal from:

unreplicated DNA unattached chromosome

Feedback signals from incomplete replicated or damage DNA that prevent the control system from passing the next checpoint until replication is complete or the damage is repaired
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FEEDBACK CONTROL

Feedback control mechanism : cells halt in S phase

Caffeine menginaktifkan mekanisme feedback control

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 repaired Protein p53 (sel mammalia) terakumulasi saat ada kerusakan DNA, sistem tertahan di G1 menahan sel masuk ke fase S dengan DNA yang rusak
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Cell Cycle in Multicellular Organism

Multiple cyclin :

Cyclins A, B, C, D, E, & F

Cdc2 ~cyclin B : induce mitosis Cdk2 ~ cyclin E : induce passage past G1 checkpoint Cdk2 ~ cyclin A : to activate the DNA replication machinery

standard vertebrate cell cycle

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Cell Cycle in Multicellular Organism

Cell growth & cell division dapat diregulasi secara terpisah penting bagi organisme multiseluler Beberapa faktor membuat sel tumbuh tetapi tidak dapat melewati G1 checkpoint & sebaliknya Sel neuron (G0) dapat tumbuh tanpa pernah membelah

Sel neuron dan sel otot : do not divide at all Sel liver secara normal membelah satu atau dua kali setiap tahun Sel-sel epitel usus membelah lebih dari 2 x sehari Sel membelah tergantung keadaan (eksternal & internal)
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Tumor-supressor gene menghambat pembentukan dan pengaktifan sistem kontrol siklus sel Proto-oncogen kebalikan tumor-suppressor gene Unrestrained proliferation hasil mutasi yang meng-inaktif-kan kedua kopi tumor-suppressor gene atau membuat satu kopi dari proto-oncogene menjadi hiperaktif
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Cell Cycle in Multicellular Organism

GF receptors activate
intracellular phosphorylation cascade change gene expression

Gen yang diinduksi oleh GF : Early response gene (myc,

fos, jun proto-oncogene)

Delayed response gene

(Cdk protein & several cyclin) requires products of the early response gene
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Cell Cycle: Multicellular Organism

Antiproliferation gene tumor suppressor gene retinoblastoma (rb) gene Loss of this gene leads to excessive cell proliferation in the immature retina (cancer in the eye of children) Dephosphorylated Rb binds to & hold inactive gene regulatory proteins
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Cell Cycle: Multicellular Organism

Gene regulatory protein (such as myc) : stimulate transcription of target genes cell proliferation Phosphorylated Rb, releasing the stimulatory proteins that activate proliferation In normal cells the Rb protein is permanently present (G0 or cycling) G0: fosfat di dalam sel sedikit, menghalangi transkripsi
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MEIOSIS Hanya untuk sel gamet :

Sperma Ovum Spora

Satu

kali replikasi kromosom/DNA Dua kali pembelahan nukleus dan sel

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Hasilnya jumlah kromosom untuk masing-masing sel anak menjadi setengahnya Sel induk : diploid (2n) 4 sel anak haploid (n)

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MEIOSIS Interfase :
phase Fase meiosis I : mirip mitosis tetapi ada modifikasi pada fase profase, yi :
Kromosom homolog berpasangan Chiasma crossing over rekombinasi

Replikasi

kromosom/DNA selama S

Fase meiosis II : tipikal pembelahan mitosis

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Growing oocyte meiosis I (single round DNA replication) meiosis II ( DNA replication) Grown Oocyte (meiosis I) is arrested : meiotic prophase ( G2 phase) just before entry into M phase
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Aksi hormon mentrigger releasing the G2 arrest M phase of meiosis I (complete) Oosit melanjutkan proses ke meiosis II becomes arrested in metaphase (mature egg)
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Fertilization releases the metaphase arrest egg completes its second meiotic division Then enters interphase of the first embryonic cell cycle
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Embryonic Cell Cycle

The shortest eucaryotic division cycles of all-shorter even than those of many bacteria are:
The

early embryonic cell cycles :

that occur in certain animal embryos immediately after fertilization Serving to subdivide a giant egg cell into many smaller cells as quickly as possible No growth occurs, G1 & G2 phases are drastically curtailed The time from one division to the next is between 8 & 60 minutes
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The standard cell cycle compared with the early embryonic cell cycle

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