Cell Division Etc

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    CELLS how it all comes together IDNA is in nucleus of cell in chromosomes

    DNA is an helix strand & is supercoiled ipackages = chromosomesHumans = 23 chromosome pairs (46 total)22 autosomes + 2 sex chromosomes

    Cells have a lifecycle cell cycle part ocycle involves replication.

    Cells must divide!If a somatic cell mitosis (to replicate)

    If a germ cell meiosis (to form gametes

    CELLS how it all comes together II

    Cells have a lifecycle (cell cycle_ part of cycle involves duplicating

    Cells must divide!If a somatic cell mitosis (to replicate)If a germ cell meiosis (to form gametes

    CELL CYCLE

    Cell cycle checkpoint (G1/S)P53 or Rb (retinoblastomaproduct) can holt cycle here ifDNA damage found

    Cell cycle checkpoint(G2/M)Cycle can Holt here ifDNA damage found

    FYI!!CHROMATID is actually one copy of all the DN

    a chromosome eg chromosome 1 these are wexist in a cell in between divisions. The familiar clooking chromosome is actually what DNA looksafter its replicated ie the cross is made of twochromatids, one copy of the other. Be careful, asterm chromosome is often used for both.

    ZoomZoomZoom

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    INTERPHASE

    Cell between divisions chromosomes NOT visibleby LM

    Consists of three phases:G1 Phase

    Growth. Metabolism,preparation for division

    S Phase

    DNA replication: chromatidsbecome chromosomes

    G2 Phase

    As G1 prepare for Mitosis

    PROPHASE

    Chromosomes condense

    Nuclear membranedisappears

    Spindle fibers appear &attach

    METAPHASE

    Centromeres of chromatidpairs line up alongmeta late of cell e uator

    ANAPHASE

    Centromeres divide &chromatids (one from eachpair) move to oppositepoles of cell

    TELOPHASE

    Nuclear envelopereappears

    Chromosomesuncondensed (chromatin)

    Spindles break up

    CYTOKINESIS

    Cytoplasmic division Cleavage furrow forms &

    progresses inwardsseparating cytoplasm intotwo

    FYI!!Sometimesintermediatephases arealsoconsidered egprometaphaseas illustrated toleft.

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    REDUCTION DIVISION (Meiosis II)Basically the same as Meiosis I

    PROPHASE I- Chromosomes condense- Nuclear envelope disappear- Chromosomes arrange in

    homologous pairsMETAPHASE II

    - Homologous pairs line up on theequator

    ANAPHASE II- members of homologous pairs

    separate with one member movingto each end

    - centromeres do not splitTELOPHASE II

    - cells now haploid cf original

    - nuclear envelope reappears- chromosomes decondense- CYTOKINESIS

    Final product:4 haploid cells all genetically different

    REDUCTION DIVISION (Meiosis I)PROPHASE 1

    - Chromosomes condense- Nuclear envelope disappear- Chromosomes arrange in

    homologous pairs- Crossing over occurs now

    METAPHASE 1- Homologous pairs line up on the

    equatorANAPHASE 1

    - members of homologous pairs

    separate with one member movito each end

    - centromeres do not splitTELOPHASE 1

    - cells now haploid cf original- nuclear envelope reappears- chromosomes decondense- CYTOKINESIS

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    DEFINITION!!Nucleoside: base + sugarNucleotide: base + sugar +phosphate

    DNA Repllication- Begins when specialized enzymes unzip DNA double he- As the two strands separate, purine & pyrimidine bases on

    each strand are exposed & are sticky, hence attract theircomplementary bases (as free nucleosides & nucleotides)from within nucleus. One strand runs in a 3-5 direction, anthe other in the opposite direction

    - The original strand of DNA with sticky ends directs the

    synthesis of a new strand of DNA through complementarybase pairing. DNA polymerase enzyme joins all thenucleotide components to one another.

    - Old strand then unites with new strand to reform a doublehelix.

    DNA polymerase joins nucleotides in a 5end-3end directiontherefore can run along one strand (leading strand) easily. Howevthe other strand requires it to run in the opposite direction. Therefothe 3-5 strand (lagging strand), is synthesized in short segments the correct 5-3 direction. These short segments placed on thelagging strand are Okazaki fragments& are ultimately joinedtogether by the enzyme DNA ligaseto form the new DNA strand.

    See picture below

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    OVERVIEW

    2 PROCESS:

    TRANSCRIPTION

    Relevant part of DNA unzipped & transcribemRNA which is single stranded & moves ouinto cytosol to Ribosomes.

    TRANSLATIONmRNA feeds through Ribsome which readsgroups of three (codons) & translates to tRNwhich goes and fetches the correspondingamino acid as determined by the genetic cod(see wheel). Ribosome then connects eachamino acid to the chain to create the proteinencoded by the gene.

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    TRANSCRIPTION

    TRANSLATION

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    Sin gl e b a s e s u b s t i t u t io nsA single nucleotide base becomes replaced by another. These single base changes are also called pointmutations. If a purine (a, t purine or a pyrimidine (c, g) pyrimidine = transition. If a purine pyrimidine orvice-versa = transversion.

    MISSENSE MUTATIONS- New base alters a codon resulting in a different amino acid

    being incorporated into the protein.

    - Eg Sickle Cell Anaemia: 17th nucleotide in gene for chainof Hb changes from AT = codon GAGGGT = sixth aachanges from GluVal altering quaternary structure of Hb =pathology!

    NONSENSE MUTATIONS- New base changes a codon from coding for an aa to a stop

    codon which causes translation of mRNA to stop

    prematurely = truncated protein unlikely to function- Occur in 15-30% of all inherited diseases incl. CF,

    Haemophilia, DMD

    SILENT MUTATIONS- Substitution of a base which causes no change in the aa &

    the final protein- Can uccur because numerous codons encode the same aa.- Only detectable by sequencing the gene

    SPLICE SITE MUTATIONS

    - Introns must be spliced out from mRNA to produce correct protein & must be very accurate- Guided by nucleotide signals at the splice sites- If a mutation alters these, the intron may not be removed = incorrect protein produced

    INSERT IONS AND DELET IONS- Extra base pairs (from a few to thousands)

    may be added or deleted for DNA of a gene- Insertions & deletions of one or two bases or

    multiples of one or two causeFRAMESHIFTS (shift in the reading frame ofthe triplet codons) = can be devastating &

    protein may be useless- Insertions or deletions of 3 or multiples of 3may be less serious as they preserve theopen reading frame- Eg Huntingtons Disease or fragile Xsyndrome both trinucleotide repeat diseases where a triplet is repeated

    CHROM OSOM A L M UT A T IONS- Any change in the structure or arrangement of the chromosomes- Occur more frequently in the crossing over stage of meiosis

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    TRANSLOCATIONS

    - the transfer of a piece of one chromosome to a non-homologous chromosome

    - They are often reciprocal, with the two chromosomesswapping segments with each other

    - Eg Philadelphia Chromosome in CML between Chr 9and 22 = abnormal hybrid gene (bcr-abl) = novel gainof function protein

    INVERSION- A region of DNA on the chromosome can flip its

    orientation with respect to the rest of thechromosome.

    DELETIONS

    - A large section of a chromosome can be deletedresulting in the loss of a number of genes.

    DUPLICATIONS- Some genes are duplicated and displayed twice on the same chromosome

    CHROMOSOME NON-DISJUNCTION- During cell division, the chromosomes fail to successfully separate to opposite poles, resulting in one of

    the daughter cells having an extra chromosome and the other daughter cell lacking one.- Can occur at Meiosis 1 or 2 producing some gametes with 2 copies of one chr. = at fertilization when

    coupled with the other parents copy totals 3.- EG Down Syndrome.

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