Chapter 3. DNA Replication & The Cell Cycle

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1 Chapter 3 DNA Replication & The Cell Cycle

2 DNA Replication and the Cell Cycle Before cells divide, they must duplicate their DNA // the genetic material DNA is organized into strands called chromosomes // humans have 46 of these strands Original cell must keep one set of chromosomes and give a complete second copy of its chromosomes to the new daughter cell // process known as mitosis since DNA controls all cellular function, this replication process must be very exact Two Laws govern cell division:

3 Principles that Allow for Accurate DNA Replication Law of Complementary Base Pairing we can predict the base sequence of one DNA strand if we know the sequence of the other enables a cell to reproduce one strand based on the information in another Law of Semi-Conservative Replication New cell will contain DNA molecule with one side new nucleotides and the other side of the DNA molecule will have half of the original DNA molecule

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5 DNA Replication Incoming nucleotides Old strand New strand Daughter DNA (e) Parental DNA (b) Replication fork DNA polymerase (a) Key DNA helicase A C T G (c) Gap in replication (d) DNA ligase

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8 Steps of DNA Replication 1. Double helix unwinds from histones 2. enzyme DNA helicase opens one short segment of helix at a time // exposing its nitrogen bases 3. replication fork the point where the DNA is opened up (like two separated halves of a zipper) 4. DNA polymerase molecules move along each strand -read the exposed bases -matches complementary free nucleotides 5. the two separated strands of DNA are copied by separate polymerase molecules proceeding in opposite directions -the polymerase molecule moving toward the replication fork makes a long, continuous, new strand of DNA -the polymerase molecule moving away from the replication fork makes short segments of DNA at a time DNA ligase joins them together

9 Steps of DNA Replication 6. from the one old parental DNA molecule, two new daughter DNA molecules are made 7. semiconservative replication - each daughter DNA consists of one new helix synthesized from free nucleotides and one old helix conserved from the parental DNA 8. new histones are synthesized in cytoplasm -millions of histones are transported into the nucleus within a few minutes after DNA replication -each new DNA helix wraps around them to make a new nucleosome 9. each DNA polymerase works at a rate of 100 base pairs per second -would take weeks for one polymerase to replicate one chromosome -thousands of polymerase molecules work simultaneously on each DNA molecule 10. all 46 chromosomes are replicated in 6-8 hours

10 Errors and Mutations DNA polymerase does make mistakes multiple modes for correction of replication errors double checks the new base pair and tend to replace incorrect, biochemically unstable pairs with more stable correct pairs result is only 1 error per 1 billion bases replicated Mutations changes in DNA structure due to replication errors or environmental factors (radiation, viruses, chemicals) some mutations cause no ill effects. others kill the cell, turn it cancerous or cause genetic defects in future generations.

11 Cell Cycle the cell s life cycle that extends from one division to the next Cell Cycle G 1 phase, the first gap phase interval between cell division and DNA replication accumulates materials needed to replicate DNA S phase, synthesis phase duplicates centrioles DNA replication occurs G 2 phase, second gap phase interval between DNA replication andcell division finishes centriole duplication synthesizes enzymes that control cell division repairs DNA replication errors Prophase G 2 Second gap phase Growth and preparation for mitosis Metaphase Anaphase S Synthesis phase DNA replication Interphase Telophase Cytokinesis G 1 First gap phase Growth and normal metabolic roles

12 M phase mitotic phase cell replicates its nucleus pinches in two to form new daughter cells Cell Cycle Interphase collection of G1, S, and G2 phases G 0 (G zero) phase cells that have left the cycle for a rest / temporary pause muscle and nerve cells / always in G zero! Cell cycle duration varies between cell types Prophase G 2 Second gap phase Growth and preparation for mitosis Metaphase Anaphase S Synthesis phase DNA replication Interphase Telophase Cytokinesis G 1 First gap phase Growth and normal metabolic roles

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14 Mitosis Cell division in all body cells (somatic cells) eggs and sperm / gametes / haploid Functions of mitosis development of the individual from one fertilized egg to some 40 trillion cells growth of all tissues and organs after birth replacement of cells that die repair of damaged tissues Four phases of mitosis prophase, metaphase, anaphase, telophase Followed by cytokinesis /

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18 1 Prophase Chromosomes condense and nuclear envelope breaks down. Spindle fibers grow from centrioles. Centrioles migrate to opposite poles of cell. Mitosis Aster 2 Metaphase Chromosomes lie along midline of cell. Some spindle fibers attach to kinetochores. Fibers of aster attach to plasma membrane. Spindle fibers Centriole 3 Anaphase Centromeres divide in two. Spindle fibers pull sister chromatids to opposite poles of cell. Each pole (future daughter cell) now has an identical set of genes. Chromatids Kinetochore 4 Telophase Chromosomes gather at each pole of cell. Chromatin decondenses. New nuclear envelope appears at each pole. New nucleoli appear in each nucleus. Mitotic spindle vanishes. Cleavage furrow Nuclear envelope re-forming Daughter cells in interphase Chromatin Nucleolus

19 Mitosis: Prophase chromosomes shorten and thicken coiling into compact rods easier to distribute to daughter cells than chromatin 46 chromosomes two chromatids per chromosome // doubled total amount of DNA one molecule of DNA in each chromatid nuclear envelope disintegrates and releases chromosomes into the cytosol

20 Mitosis: Prophase (cont.) centrioles sprout elongated microtubules the spindle fibers push centrioles apart as they grow pair of centrioles lie at each pole of the cell some spindle fibers grow toward chromosomes and attach to the kinetochore on each side of the centromere spindle fibers then tug the chromosomes back and forth until they line up along the midline of the cell

21 Mitosis: Prophase Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 Prophase Chromosomes condense and nuclear envelope breaks down. Spindle fibers grow from centrioles. Centrioles migrate to opposite poles of cell. 1

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23 Mitosis: Metaphase Chromosomes are aligned on cell equator oscillating slightly and awaiting signal that stimulates each of them to split Mitotic spindle lemon-shaped array of spindle fibers long spindle fibers (microtubules) attach to chromosomes shorter microtubules (aster fibers) anchor centrioles to plasma membrane at each end of cell

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25 Mitosis: Anaphase Begins with activation of an enzyme that cleaves two sister chromatids apart at centromere Daughter chromosomes migrate towards each pole of the cell with centromere leading the way motor proteins in kinetochore crawling along the spindle fiber as the fiber itself is chewed up and disassembled at the chromosomal end Each daughter cell following mitosis are genetically identical

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27 Mitosis: Telophase chromatids cluster on each side of the cell rough ER produces new nuclear envelope around each cluster chromatids begin to uncoil and form the chromatin remaining mitotic spindle breaks up and vanishes each nucleus forms nucleoli this indicating it has already begun making RNA and preparing for protein synthesis

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29 Cytokinesis the division of cytoplasm into two cells telophase is the end of nuclear division but overlaps cytokinesis early traces of cytokinesis visible in anaphase achieved by motor protein myosin pulling on microfilaments of actin in the terminal web of cytoskeleton creates the cleavage furrow around the equator of cell cell eventually pinches in two

30 Timing of Cell Division Cells divide when: they have enough cytoplasm for two daughter cells they have replicated their DNA adequate supply of nutrients are stimulated by growth factor chemical signals secreted by blood platelets, kidney cells, and other sources neighboring cells die, opening up space in a tissue to be occupied by new cells

31 Timing of Cell Division Cells stop dividing when: when nutrients or growth factors are withdrawn snugly contact neighboring cells / no room for new cells contact inhibition the cessation of cell division in response to contact with other cells

32 Meiosis Haploid cell division Type of cell division seen only in the formation of gametes // in gonads // females = ovaries produce eggs // males = testes produce sperm Reduce chromatin from 46 chromosomes to 23 chromosomes Sperm and egg unite to form a zygote with 46 chromosomes

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