K6- Replikasi DNA

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    as c

    Science

    Departemen

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    The nucleus contains a blueprint for all cells structures & activities

    encoded in DNA

    The information that makes each individual life unique must be

    preserved & then passed on to progeny

    Cells divisions does not stop with the formation of mature organism

    but continous in certain tissues throughout life

    New cells originate from other living cellscells division

    More than 1013cells form a human bodythe whole organism has

    been generated by cell divisions from a single cell

    One of the hallmarks of life is its ability to reproduce

    Introduction

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    Tissues of the body divided into three

    groups base on proliferative activity

    of their cells:

    Continuously

    dividing tissues

    (labile tissues)

    Quiescent

    tissues (stable

    tissues)

    Nondividing

    tissues

    (permanent

    tissues)

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    Example:

    Surface epithelia

    i.e. stratifiedsquamous

    epithelia of skin,

    oral cavity, vagina& cervix

    The lining mucosa

    of all excretoryducts of glands

    (e.g., salivary

    glands, pancreas,biliary tract)

    The columnar

    epithelium of the

    GI tract & uterus

    The transitionalepithelium of urinary

    tract, and cells of

    bone marrow &

    hematopoietic

    tissues

    Cells proliferate throughout life Replacing that destroyed

    Continuously dividing tissues (labile tissues):

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    Example :

    Parenchymal cells of

    liver, kidneys, &

    pancreas

    Mesenchymal cells

    such as fibroblasts &

    smooth muscle

    Vascular endothelial

    cells; & lymphocytes

    & other leukocytes

    Normally have a low level of replication but cells can undergo rapid

    division in response to stimuli & capable of reconstituting the tissue

    of origin

    Quiescent tissues (stable tissues)

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    Example : neurons & skeletal & cardiac muscle cells

    Contain cells that have left the cell cycle & cannot undergomitotic division in postnatal life

    Nondividing tissues(permanent tissues)

    t

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    ynt es s occurs ns e

    the nuclues

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    Cell nucleus contain 3 major components:

    Nuclearenvelopecomposed of two

    parallel unit membranes that fuse witheach other at certain regions to form

    perforations known as nuclear pores

    Chromatin: a complex of DNA and

    proteins and represents the relaxed,

    uncoiled chromosomes of the interphase

    nucleus

    Nuclelolus: the deeply staining-non

    membrane bounded structure within

    nucleus that is involeved in rRNA synthesisand in the assembly of small and large

    ribosomal units

    CELL NUCLEUS

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    Chromatin: a complex of DNA and

    proteins and represents the relaxed,

    uncoiled chromosomes of the interphasenucleus

    DNA: the cells genetic material

    Like a computer tape that stores many

    programs

    DNA present in each cell in the form of anumber of chromosomes

    Chromosomesare chromatin fibers that

    becomes so condensed and thightlycoiled during mitosis and meiosis that

    they become visible with the light

    microscope

    Chromatin

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    Chromatin Depending on

    transcriptional activity:

    Heterochromatin:

    Condensed inactive form of chromatin

    Located mostly at periphery of nucleus

    Euchromatin:

    Active form of chromatin where the

    genetic material being trancribed intoRNA

    Composed of thread like material 30

    nm thick: Nucleosomes: unwound material

    resembling beads on stringconsist

    of histone

    DNAmoleculesthin filament

    resembling string

    Chromatin contd

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    The Nucleus

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    Chromatin-Histone

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    Genome: is total number of genes within one mature cell (60 -

    100.000).

    Genes:

    Basic unit of genetic information.

    They determine the inherited characters

    Each gene is a part of DNA sequences that contains genetic information

    coding for synthesis of a certain protein

    Chromosomesstorage units of genes.

    Most human cells contain 46 chromosomes:

    22 pairs of chromosomes , named autosomes.

    1 pair of sex chromosomes (X and Y):

    XYin males, XXin females

    Genom & Gene

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    Interphase (G1-S-G2)

    may extend for days,

    weeks or longer

    depending on the celltype

    M phaseusually lasts

    only an hour or so

    S PHASE

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    DNA contains all informations for human.

    Before any cell division, a cell must duplicate all its DNA.Replication occurs during S phase of cell cycle (synthesis

    phase of interphase)

    Cells also synthesize the additional histones (needed asthe cells double the nucleosomes in its chromosomes)

    S-PHASE

    DNA R li i

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    DNA Replication

    Replication means making a

    replica(an exact or identicalcopy)

    DNA replication is the process of

    making an exact copy of DNA byusing one of the parent DNA

    strands as templateThe

    original DNA strands are used as

    templates for the synthesis of

    new strands

    DNA functions to :

    Store genetic information &

    transferring it to daughter cells during

    mitosis by replication &

    Transferof genetic information from

    DNA to RNA to be expressed as

    proteins

    It occurs very quickly, very

    accurately and at the appropriate

    time in the life of the cell

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    Models of DNA Replication

    In the late 1950s, three different

    mechanisms were proposed for the

    replication of DNA

    Conservative

    model

    Both parental

    strands stay together

    after DNA replication

    Semiconservative

    model

    The double-stranded

    DNA contains one

    parental & one

    daughter strand

    following replication

    Dispersive model

    Parental & daughterDNA are

    interspersed in both

    strands following

    replication

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    Models of DNA Replication

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    replication

    1. Semi-conservative mode2. Ordered and sequential

    3. Semi-discontinuous

    One strand synthesized continuously(Leading strand)

    Other strand synthesized

    discontinuously ( Lagging strand)

    Fragments called Okazaki fragments

    4. Accurate

    5. Bi-directional

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    Three Steps for Replication

    1. Initiation

    2. Elongation

    3. Termination

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    DNA template

    Nucleotides : A ,T & G, and C

    RNA primers

    Enzymes

    DNA Helicase

    RNA polymerase ( Primase)

    DNA polymerases

    Topoisomerase I , II

    Ligase

    Some Additional factors

    SSB proteins (Single-strand binding proteins (SSBs)

    Requirements

    DNA l T

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    DNA Ploymerase

    Synthesis of lagging strand & gap filling

    DNA polymerase

    DNA repair

    DNA polymerase

    Mitochondrial DNA synthesis

    DNA polymerase Synthesis of leading strand

    DNA polymerase

    DNA repair

    DNA polymerase Types

    rep ca on s n a e a or g ns

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    rep ca on s n a e a or g nsof replication

    Hetereochromatin replicateslater in S Phase than

    euchromatin Replication initiated at

    multiple points known asReplications origins

    DNA double helix is split open

    by DNA helicase to expose thebase sequences

    The resulting separation ofDNA strand are calledReplication bubbles

    Two replication complexesform at each origin. One ateach end of the bubble and isa Y-shaped structure calledReplication fork

    DNA R li ti I iti ti

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    The two DNA strands are separated

    SSB proteins stabilize the single stranded DNA

    Two replication forks are created

    Each strand acts as a template

    Replication proceeds from 5 to 3 end

    DNA Replication Initiation

    DNA El ti

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    1. DNA polymerase clamps to the leading strand & adds DNA

    nucleotides to the RNA primer2. DNA polymerase proofreading activity checks and replaces

    in correct bases

    3. Continous (Leading) strand synthesis produces new

    fragments on the 3to 5 template but in a 5 to 3

    direction

    4. Discontinous (lagging) strand synthesis produces okazaki

    fragments but in 5 to 3 direction5. Replication proceeds along the single strands about 40-50

    nucleotides persecond simultaneously in both directions

    6. DNA Ligasejoined Okazaki fragment together

    DNA Elongation

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    Replication orientation: 5 3

    Movement of Replication fork

    3

    553

    35

    3

    5

    Okazaki fragment

    Leading strand

    (continous)

    Lagging strand

    (discontinous)Replication fork

    1. Continous (Leading) strand synthesis produces new fragments on

    the 3to 5 template but in a 5 to 3 direction

    2. Discontinous (lagging) strand synthesis produces okazaki fragments

    but in 5 to 3 direction

    3. Replication proceeds along the single strands about 40-50

    nucleotides persecond simultaneously in both directions

    4. DNA Ligasejoined Okazaki fragment together

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