Exam Three Bio - Ch 12, 13, 14, 15

Mitosis - the only way to get new genetically identical cells

  • somatic cells - normal body cells

meiosis - produces genetically different daughter cells galled gametes responsible for reproduction

chromosome - single long DNA strand wrapped around histones and containing genes

  • one chromosome has many genes, which code for products

unreplicated chromosome → replicated chromosome → condensed replicated chromosome

  • even when chromosomes copy, if they are attached to each other they are one chromosome; this is known as sister chromatids, which remain joined at the centromere until they are separated during cell division.

m-phase: mitosis or meiosis

interphase: gap 1, s-phase, gap 2

  • these contain checkpoints to ensure cell properly divides

  • chromosome NEVER changes during mitosis

prophase - chromosomes condense, spindles form

  • spindles are made of microtubules and are able to move chromosomes and pull chromatids apart

  • centrioles move to opposite ends of the cell

prometaphase

  • nuclear envelope breaks so microtubules can attach to chromosomes at kinetochores

  • kinetochores are structures on the centromere of sister chromatids

  • they are proteins providing a site of connection

metaphase - central alignment of chromosomes

  • spindle fibers move chromosomes to metaphase plate and are anchored to cell membrane

anaphase

  • microtubules shorten and pull sister chromatids apart, ensuring each daughter cell receives the same number of chromosomes

  • because sister chromosomes are not attached, they are now called chromosomes

telophase

  • reformes nuclear envelope and chromosomes recondense in each daughter cell

  • each daughter cell now has unreplicated chromosomes

cytokinesis - splitting of cytoplasm

  • plants build a new cell wall with their cell plates

  • animals just split membrane in half

    • this process happens with actin and myosin proteins, creating cleavage furrows

prokaryotic division - binary fission

  • prokaryotes do not have nuclei or spindle fibers

  • replicate circular chromosomes and undergo the same process

chromosomes

  • homologs - chromosomes of same size and shape with same genes in same place

  • sister chromatids - identical PART of a chromosome

  • non-sister chromatid - one chromatid is on one homolog and a separate chromatid is on a different homolog

meiosis - goal of halving chromosomes and producing gametes

  • increases genetic diversity

  • chromosome number is restored during fertilization

  • all organisms have a specific number of chromosomes unique to them

  • x and y are sex chromosomes

  • chromosome pairs that do not determine sex are called autosomes

  • homologous chromosomes: NOT identical

  • bivalence: paired, replicated homologs attached during prophase I

ploidy

  • number of chromosome pairs

  • n is the number of unique chromosomes in a cell

  • haploid: meaning single form, denoted by n, one distinct type of chromosome

  • diploid: meaning double, denoted by 2n, one paternal and one maternal chromosome

  • polyploidy: 3 or more of each unique chromosome

  • ploidy changes throughout an organisms life cycle

    haploid gametes combine to form diploid zygotes

  • then diploid zygotes undergo mitosis and develop into diploid adults

priori to meiosis

  • chromosomes always replicate in s-phase

  • checkpoints remain the same and now pairing matters

two complete cell divisions

  • meiosis 1: homologous chromosomes separate

  • meiosis 2: sister chromatids separate

meiosis 1 - promoting genetic variation via crossing over, creating new allele combinations

  • prophase 1 - undergoes synapsis, create chiasmata, and complete crossing ober

    • homologs come close together and become bivalent during synapsis

    • chiasmata - non-sister chromatids join and prepare to cross over

    • crossing over - non-sister chromatids exchange genetic information at genes / alleles

  • metaphase 1 - homologs line up at the metaphase plate

  • anaphase 1 - homologous pairs separate into individual replicated chromosomes

    • crossing over - genetic recombination

    • independent assortment - the way homologs align at metaphase plate

    • fertilization - union of two random gametes

      • outcrossing and self pollination

Nondisjunction - either homologs or sister chromatids fail to separate

  • aneuploidy - cells have an abnormal amount of chromosomes

  • if nondisjunction occurs in meiosis 1, two n+1 cells and two n-1 cells are produced

  • karyotype: visualization of all chromosomes to find aneuploidy

    • trisomy-21: three chromosomes are at chromosome 21, cause of down syndrome

cell cycle regulation

  • checkpoints cause cell to stay in that phase until it’s ready for division

  • g1: is the cell large enough, does it have enough nutrients, are social signals present and is the DNA undamaged?

    • g0: mature / unfixable cells never pass through this checkpoint

  • g2: have the chromosomes been successfully replicated and is the DNA undamaged?

  • m-phase

    • checkpoint between prometaphase and metaphase ensuring spindle fibers properly attached and the chromosomes properly separate

proteins

  • cyclins: only produced when needed in a specific part of the phase

    • at G1, G1 to S phase, S phase and M phase

    • work with cyclin-dependent kinases (cdks)

    • only work when paired with cyclin

    • activate protein by removing phosphate from ATP and donate to a specific protein

  • MPF: m-phase promoting factor

    • cyclin and cdk pair in the cytoplasm telling the cell it’s ready for mitosis

    • cyclin is produced in g1 and peaks during m-phase

      • binds to cdk and activates it, cycling concentration goes down until the cell is ready for another cycle

regulation of MPFs

  • interphase

    • cyclin concentration increases and attaches to cdks

    • cdk has an extra phosphate attached, preventing it from activating the cycle

  • G2

    • phosphate group is removed and activates cdk

  • m phase

    • cyclin degrades and cdk becomes inactive once division begins

G1 checkpoint

  • controlled by growth factors

    • hormones promoting the cycle like gas

  • tumor suppressors

    • restrict cell division like brakes

    • p53: DNA repair

    • Rb: prevents G1 from transitioning to S-phase

  • E2F - activates s-phase

    • must be held back until cell is ready

    • growth factor produced cyclin and E2F

    • Rb inhibits e2F

    • cyclin binds to cdk, which is inhibited by phosphate

    • phosphate is removed from cdk by an enzyme, cdk removes phosphate from ATP and attaches it to the Rb and inactivating it

    • once rb is inactive, E2F is released and kicks off the cycle

Cancer

  • caused by too many growth factors, too much phosphate enzyme, too much e2f

  • also by too much cyclin or mutated Rb

  • cancer is many diseases caused by uncontrolled cell division

    • invades nearby tissue and metastasizes

  • tumor - mass of uncontrolled cells

    • benign: noncancerous and noninvasive mass

    • malignant: metastasizing cells

    • driver genes

      • protooncogenes - promote cell growth and division by coding for growth factors

      • oncogenes - mutated alleles causing uncontrolled division

      • too many of either of these cause cancer

  • tumor suppressors also can mutate or be broken, causing cancer

Growth Factors

  • tell the cell to create e2f and cyclin

  • RAS - gene involved in many cancers

    • part of signal transduction pathway that tells cell to produce e2f

    • when mutated, RAS never inactivates and/or tells cell to activate without growth factor

  • p53 - cell cycle control and DNA repair

    • transcription factor

    • DNA damage sets off signaling pathway, p53 tells nucleus to stop cycle until the dna is repaired

    • defective or missing p53 leads to uncontrolled division

Genetics

  • one gene mutation usually isnt enough to cause cancer

    • one oncogene and many tumor suppressor defects must be present

  • genetic predisposition: increased likelihood of developing a specific cancer

    • individuals inherit one broken copy and only need to have one more mutation to develop cancer

  • BRCA: two copies of every gene, individual inherits one of them, it only takes one more mutation to get cancer

environmental factors

  • carcinogens - substances proven to cause cancer

    • tobacco, alcohol, UV, pollution

  • cancer is treated with surgery, chemo, radiation, targeted therapy and immunotherapy

Gregor Mendel - father of modern genetics

  • inheritance of traits

  • traits are passable parts of an organism

blending inheritance hypothesis - organism’s traits mix together to make a combination phenotype

  • black sheep + white sheep equals gray sheep

inheritance of acquired characteristics - whatever trait is used a lot gets passed on

  • giraffes reach for leaves, so each subsequent generation has slightly longer necks

peas as a model organism

  • practical to work with, conclusions apply to many other plants

  • short growth and development time, cheap

  • can self and cross fertilize

  • perfect control over what genes come from which parents

polymorphic traits: have two or more varieties of the gene

  • seed shape and color, pod shape and color, flower color and position, stem length

    • peas have many observable traits to be studied

  • Mendel took specific plants with distinct traits and crossed them

    • round + wrinkled seeds produced round seeds, which is how he discovered dominant and recessive traits

    • pure line or true breeding plants self-fertilize

    • hybrid - offspring differs from parent traits

    • F1 - first generation of hybrid children, then self-fertilize to see what happens

  • particulate inheritance: traits are controlled by discrete, unchanging particles

    • something must be controlling heredity

    • Mendel’s particles are now called genes

    • allele - responsible for dominant or recessive triats

      • genes are DNA sequences on chromosomes

    • phenotype: what you can see

    • genotype: the genes determining phenotype

  • heterozygous - means differently joined, contain both dominant and recessive alleles

  • homozygous - means same joined, contains either only dominant or only recessive alleles

  • principle of segregation: alleles separate during meiosis

    • each gamete contains one allele of every gene

    • diploid: 2 alleles

    • haploid: 1 allele

      • happens during Anaphase 1 of meiosis 1

  • principle of independent assortment

    • unlinked genes

    • alleles separate independently of each other

    • happens during metaphase of NON-HOMOLOGOUS chromosomes

    • when alleles line up, what an allele does has nothing to do with any other alleles

Thomas Morgan: used fruit flies as model organisms

  • reproduce quickly and in large numbers

  • small, hard to kill

Wild Type: most common phenotype, doesn’t need to be dominant or recessive

Mutant: unusual phenotype resultant of mutation on gene

Morgan’s goal was to find mutants in fruit flies and experiement with them

discovered the reciprocal cross

  • using same phenotypes but switching the parent they are on

Sex-Linked Inheritance: exception to Mendel’s rules

  • sex chromosomes separate males to form X and Y bearing gametes

  • X-linked traits

  • 50% sperm contain X chromosomes and 50% contain Y

  • helps to only look at males since they only have one X chromosome, and they always express the X linked trait

    • you can tell a trait is sex-linked if the reciprocal cross gives different phenotypic ratios

Linked Traits: two genes on the same chromosome

  • NOT independent assortment

  • allles are linked together

  • example: chromosome is RrYy, linked trait would mean it could only either be Ry or rY

Linkage and Genetic Mapping

  • distance between genes determines frequency of crossing over and therefore new genes

  • Genetic map: physical map of where genes are on the chromosome

    • determines recombination frequency

    • distances calculated in centimorgans

autosomal dominant: mutated gene on ONE chromosome is enough to affect offspring

autosomal recessive: both parents must carry the gene on their respecitve chromosomes

x-linked dominant: trait shows up in all daughters when father is affected

x-linked recessive: trait shows up in all sons when mother is affected

pedigrees:

  • male: square

  • female: circle

  • fully black: carries both alleles for trait

  • half black: carries one allele for trait

  • traits MUST be recessive if they skip a generation

DNA replication

  • semiconservative: parental strands separate and each one is used as a template for synthesis of a daughter strand

  • conservative: parental strands

DNA polymerase

  • how replication is carried out

  • DNA polymerases ONLY proceed 5’ to 3’

    • existing 5’ end, adding new nucleotides fo 3’ end

    • there must already be an existing 3’ OH group to stick new nucleotides onto it

    • there must be a template strand that tells the polymerase what base goes where

  • Bacteria - 5 types of DNA polymerases, DNA I - V

  • Eukaryotic - 14 types, DNA alpha - nu and sigma

  • carry out replication, repair, or both

the energy for this process comes from deoxyribonucleoside triphosphates - dNTPs

  • dATP, dGTP, dTTP, dCTP

  • lowercase d indicates we are discussing DNA not RNA

  • ATP regularly used for energy is an RNA nucleotide

replication ALWAYS proceeds 5’ to 3’

  • 3’ end with -OH group for new nucleotides to be added

  • template strand so polymerase ‘knows’ what base to add

    • when the polymerase is adding the base, there is only one base that will fit there due to the hydrogen bonding

    • for example, only guanine can attach to cytosine due to the functional groups on the ends of nitrogenous bases

    • dGTP → triphosphates provide energy used to attach G purine to C pyrimidine

      • dehydration reaction: water is lost, plus releasing two phosphate groups and energy

Origin of Replication

  • in bacteria, very specific sequence

  • bacteria only have one circular chromosome so DNA replication is different than in eukaryotes

  • one origin of replication on the chromosome

    • 2 DNA strands are separated, where this occurs is called a replication bubble

    • replication proceeds 5’ to 3’ in both directions

    • 1 new DNA strand is being built around the left side of the circle, and one is being built around the right side

      • clockwise and counterclockwise

  • eukaryotes have many simultaneous origins

    • replication fork: new DNA must stay parallel to what is already there

      • at the top strand, new DNA is being built towards the replication fork

      • at the bottom strand, DNA is being built away from the replication fork, opposite the top strand

        • new region of single-stranded DNA, so the process has to catch up to the first strand

      • anti-parallel causes the secondary structure to form and create the double helix

  • top strand: continuous or leading strand

  • bottom strand: discontinuous or lagging strand

    • every time the DNA opens up, this process has to be restarted and the DNA is ‘lagging’ behind

Helix Opening / Stabilized

  • helicase: enzyme opening double helix and separating two strands

    • if they were left opened, the DNA strands would base-pair back together

      • SSBPs: bind to single stranded DNA and prevent it from closing back up

        • single strand DNA binding proteins

  • topoisomerase: straightens DNA so helicase can easily separate the strands

    • takes the supercoiled DNA and relaxes it

  • primase: initiates DNA synthesis

    • is an RNA polymerase

    • doesnt require the free 3’ -OH to build from

    • primase attaches to the DNA and just starts putting RNA onto the DNA, DNA is built with RNA, and then after the process is over, DNA replaces RN

Leading Strand Synthesis