Cellular Perspectives test #4

Chromatin

material that makes up the chromosomes of eukaryotes - DNA - + protein

Chromatid

chromatids only exist in pairs (sister chromatids)

chromosomes in eukaryotic cells

• becomes visible when chromatin is condemned

• occurs after DNA duplication (cell preparing to divide)

1 pair of sister chromatids are..?

counted as 1 chromosome

cell division

• ability of organisms to produce more of their own kind of best distinguishes living things from nonliving matter

• the continuity of life is based on the reproduction of cells or, cell division

all cells arise form..?

the division of pre-existng cells

cell division roles

• asexual reproduction

  • reproduction of an entire single celled organism

  • production of some multicellular organisms

  • growth from a fertilized egg into an adult

  • repair and replacement of cells in an adult

• sexual reproduction

  • sperm and egg production

most cell division results in genetically identical daughter cells

• distribution of identical material - DNA - to two daughter cells

• no completely identical cells, though

mitosis

division of cell nucleus

mitosis in plant cells

1. prophase

2. prometaphase

3. metaphase

4. anaphase

5. telophase

cytokinesis

comparison of animal and plant cells

plaidy (n= # unique chromo)

• refers to the # of complete chromosomes sets present

  • a non dividing eukaryotic cell typically has 2 sets of chromosomes ( diploid, 2n)

after mitosis, both daughter cells have some plaidy as parent cells

• n → n haploid

• 2n → 2n diploid

• 3n → triploid

• 6n → 6n hexaploid

consequence of mitosis

daughter cells have a complete set of chromosomes; if they are genetically identical to each other and to the parent cell, they are not completely identical

mitosis division results in genetically identical daughter cells

• distribution of identical genetic material - DNA - to 2 daughter cells

• not completely identical daughter cells

binary fission in prokarytoes

• prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission

• the single chromosomes replicates, beginning at the origin of replication

• the 2 daughter chromosomes actively move apart while the cell elongates

• the plasma membrane pinches inwards, dividing the cell into 2

• prokaryotes reproduce by binary fission

binary fission means “dividing in half”

• occurs in single celled organism

• 2 identical; cells arise from one cell

• is very fast, for example. E.coli can divide every 20 minutes

process of binary fission

1. chromosome replication begins

2. one copy of the origin is now at each end

3. replication finishes

4. 2 daughter cells result

some eukaryotes also do a form of binary fission

• amoeba

• paramecium

• other protists

• still do mitosis to divide nucleus

evolution of mitosis

• since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission

• certain protists ( dinoflagellates, diatoms and some yeasts) exhibit types of cell division that seem intermediate between binary fission and mitosis

heredity meiosis

transmission of traits from one gene → next

meiosis heredity genes

units of heredity, made up of segments of DNA passed to the next gene via reproductive cells: gametes (sperm/eggs)

homologous chromosomes

• each gene has a specific position (locus) on a certain chromosome

• each organism has a unique # of chromosomes - the match set are called homologous

gametes

only types of human cells produced by meiosis, rather than mitosis

meiosis: getting half the # of chromosomes

• only in sexually reproducing organisms (needed to gametes)

• need 2 rounds of cells division

• results in 4 daughter cells, each with ½ the genetic material of the original cell

• each has at least 1 copy of each chromosome

meiosis

the division of the nucleus with reduction in chromosome number

• still apart of cell cycle

• DNA replication still takes place in S-phase

ploidy & meiosis: only even ploidy cells can undergo meiosis the daughter cells will be:

• diploid cell (2n) → n (haploid)

• triploid (3n) → x

• tetraploid (4n) → 2n (diploid)

• hexaploid (6n) → 3n (triploid)

• humans:diploid with 45 chromosomes & n=23

• wheat: hexaploid with 42 chromosomes & n=7

stages of meiosis

• meiosis 1: homologous chromosomes separates

  • results in 2 haploid daughter cells with replicated chromosomes called reductional division

• meiosis 2: sister chromatids separate

  • results in 4 haploid daughter ells with unreplicated chromosomes called equational division

prophase 1

• > 90% of the time required for meiosis

• chromosomes coil and become compact

• homologous chromosome come together as pairs by synapsis aligned gene by gene

• each pair with 4 chromatids, is called a tetrad

• non sister chromatids exchange genetic material by crossing over

independent orientation at metaphase 1

• each pair of chromosomes independently aligns

• equal probability of the maternal or paternal chromosomes facing a given pole

• the # of combos for chromosomes packages into gametes is 2^n where n=haploid # of chromosomes

• random fertilization of each unique egg with each unique sperm

homologous chromosomes can carry different versions of genes:

seperation of homologs during meiosis can lead to genetic differences between gametes since homologs move to opposite poles during anaphase 1, gametes will receive either the maternal or paternal version of the gene

genetic recombination

• production of new combos of genes

• crossing over → exchange of genetic material between homologous chromosomes

  • non sister chromatids join at a chiasma

  • corresponding amounts of genetic material are exchanged between maternal and paternal(nonsister) chromatids

chiasma

the site of attachment and crossing over only in meiosis

mutations

change in the nucleotide sequence of DNA

base substitutions

replacement of one nucleotide with another

• effect depends on whether there is an amino acid change that alters the function of the protein

deletions or insertions

• alter the reading frame of the mRNA, so that nucleotides are grouped into different codons

• lead to significant changes in amino acid sequence downstream of mutation

• cause a nonfunctional polypeptide to be produced

due to redundancy in the genetic code

• some changes are silent or synonymous

• some are close enough in composition that the change does not affect the final protein-missense but conservative

cancer

type pf growth in which some cells divide and accumulate in an uncontrolled way

tumor

the resulting mass of tissue

tumors arise

the crucial issue is not the rate of division but rather the balance between cell division and cell differentiation or cell death

• cell differentiation is the process by which cells acquire specialized properties

• as cells acquire these specialized traits, they often lose the capacity to divide

disruption in balance

• in tumors, cell division is uncoupled fro cell differentiation and death

• some cell divisions give rise to 2 cells that can both continue to divide

• reagardless of how fast or slow the cells divide, the tumor will continue to grow as new cells are produced in greater numbers than needed

carcinogenesis

multistep process that converts normal cells → cancer cells

the hallmarks of cancer

• cancer cells develop a group of 5 traits, these traits are common to all forms of cancer, but each trait can be acquired differently

1. self sufficiency in growth signals

2. insensitivity to antigrowth signals

3. evasion of apoptosis

4. limited replicative potential

5. sustained angiogenesis

6. tissue invasion and metastasis

self sufficiency in growth signals

• cells do not normally proliferate unless stimulated by a growth factor

• cancer cells escape this requirement through action of oncogenesis

  • proto-oncogenes are normal cellular genes

  • where as oncogenes are mutated genes that can cause cancer by making cells grow out of control

insensitivity to antigrowth signals

• normal tissues are protected from excess proliferation by growth inhibiting mechanisms

• cancer cells evade such antigrowth signals (ex. density dependent inhibition of growth)

• normal cells grown in culture divide until the surface pf the vessel is covered by a single layer of cells

• once this monlayer stage is rached, cell division stops, called density dependent inhibition of growth

density dependent inhibition of growth

cancer cells will continue to divide and pile up upon one another lacking sensitivity

evasion of apoptosis

• cancer cells evade apoptosis, which normally destroys cells with genetic damage

• for some cancers, uncontrolled growth is due to a failure to undergo apoptosis, rather than to increased cell division

• this often brought about by mutations in the p53 gene

what causes cancer

• cancers are commonly caused by random errors in DNA replication and repair, environmental agents, lifestyle factors, and hereditary

• cancer is also a genetic disease, in which cells that have acquired mutations progress toward proliferation and metastasis

errors in DNA replication or repair explain many cancers

• a major explanation for cancer lies in failures in FNA replication or repair

  • these tumors show no correlation between a patients environmental or lifestyle and the tumor

• the number of stem cells division and the lifetime incidence of cancer in those tissues is correlated

• there is an additive effect between increased innate mutations and conditions like cell stress of chemical exposure

inborn errors explain some cancer

• humans inherit 50-1100 mutations from their parents at birth

  • most of these mutations do not occur in protein coding regions, of those that do, only a few are in genes that promote cancer

• however, some hereditary mutations lead to higher incidence of cancer, including those that control cell proliferation or DNA repairs

• any new mutations act on this background

many chemicals can cause cancer

• mutagens are any physical, chemical, or biological agent that permanently alters genetic material-usually DNA

• carcinogens are cancer causing agents

  • many carcinogens share a need for metabolic activiation before they can cause cancer

precarcinogens

• substances that must be metabolically activated before causing cancer are called pre-carcinogens

  • most are activated in the liver by memories of the cytochrome p450 enzyme family

• these catalyze the oxidation of foreign chemicals to make them less toxic and easier to eliminate from the body

DNA changes and genes

• DNA mutations involved in cancer generally affect genes that control cell proliferation and survival

• the 2 main classes of affected genes are oncogenes and tumor suppressor genes

oncogenes

• an oncogene is one whose presence can trigger the development of cancer

  • can be introduced to the cell by cancer causing viruses

  • can arise from mutation of normal cellular genes

• oncogenes encode proteins that stimulate excessive ccell proliferation and/or promote cell survival by inhibiting apoptosis(cell death)

• a single oncogene is generally not sufficent to cause cancer

  • multiple mutations are usually required to convert a normal cell into a cancer cell

converting proto-oncogenes into oncogenes

• if and when the structure of the proto-oncogene is altered, the mutated form can cause cancer

tumor suppressor genes

• the loss or inactivation of tumor suppressor genes can lead to cancer

  • the normal function of such genes is to restrain cell proliferation

• tumor suppression is observed even when the original cells possessed an oncogene

• tumor suppressor genes can be identified in families with heritable forms of cancer; they have increased susceptibility to cancer

the two hit hypothesis

• increased cancer susceptibility is usually inherited defect in a tumor suppressror gene

• two successive mitatoons in the same gene would be required to produce a loss of cuntion in a tumor suppressor gene

• if people inherit a mutation in one copy gene, there is a greater chance of sustaining a second mutation in the gene:the 2 hit hypothesis

• an inactivating mutation in the second copy of a tumor suppressor gene can lead to cancer

Rb

• the RB gene product is required to prevent cells from passing through the G1 restriction point without an appropriate signal from a growth factor

• mutations in the gene disrupt the normal controls on cell proliferation; this effect is also seen in other types of cancers

p53 tumor suppressor gene is the most frequently mutated gene in human cancers

• the p53 febe is mutated in about 50% if cancers

• DNA damage stimulated the p53 pathway, which triggers cell cycle arrest and apoptosis

• p53 gene disruption causes failure of apoptosis that contributed to cancer development by allowing survival and reproduction of cells with DNA damage

categories of tumor suppressor genes

• genes like RB and p53 are called gatekeeper genes

  • their loss opens the gates to excesssive cell proliferation

• genes involved in DNA repair and chromosomes sorting are called caretaker genes because they maintain genetic stability

cancers develop by stepwise accumulation of mutations incolving oncogenes and tumor suppressor genes

• cancers almost always exhibit mutations in multiple genes

  • for a given type of cancer, there are typically mutations in 50-75 different protein coding genes

  • mutations rates in cancer cells are hundreds or thousands of times higher than normal

  • a small number are mutated frequently in the same types of cancers of many different patients, whereas the rest are infrequently mutated

stepwise model for the genetic development of colon cancer

1. normal cells

2. early benign tumor

3. intermediate benign cancer

4. late benign tumor

5. localized cancer’invasion and metastasis