7. Chromosomes Flashcards
Chromosomes
- term coined in 1880’s: coloured bodies
- carriers of genetic info
- during S phase, chromosomes duplicate and form dyads
- the attached duplicated chromosomes are called sister chromatids
- ploidy indicates the number of sets of chromosomes
Ploidy
- most animals are diploid- have two copies of each chromosome, one from the mother and one from father
- gametes are haploid- have one set- arise through meiosis
diploid number
2n
number of chromosomes per somatic (body) cell
Haploid number
n number of chromosomes in gametes -humans 2n=46 (22 autosomes and 2 sex chromosomes) -mouse 2n=40 -drosophila 2n=8
aneuploidy
abnormal number of chromosomes
examples of aneuploidy?
trisomy= one extra chromosome
monosomy=missing chromosome
nondisjunction
- meiosis I starts normally; tetrads align at metaphase
- one set of homologs fails to separate
- meiosis II occurs normally
- all gametes have abnormal number of chromosomes
Chromosomes are NOT indestructible!
-can be broken and when repaired they may get scrambled.
translocations
movement to new chromosome
inversions
portion of chromosome is flipped
deletions
section of DNA excised
insertions
section of DNA inserted
translocations are the transfer of a piece of one chromosome to a _____________ chromosome
nonhomologous
translocations can result in change in phenotype by:
- breaking a gene
- moving gene to a region where it can be controlled by another regulatory sequence
- creating hybrid gene
(can elongate one side of chromosome)
Some cancers are due to translocations?
CML chronic myelogenous leukemia
-the c-abl gene encodes a kinase that regulate cell proliferation; the translocation alters the controls of this gene, placing it under the control of another gene’s bcr promoter
Translocation distinguishes human and ape karyotypes
- apes=48 chromosomes
- humans = 46 chromosomes
- genes in humans and chimps differ by
centromeres
the constricted central portion of each chromosome
- the DNA contains alpha satellite DNA; made of non-transcribed 171 base repetitive sequences
- repeated 1000s of times
- attach to the kinetochores during M phase
telomeres
-non coding regions at the ends of the chromosomes
-short repeated sequence: repeated 500-5000X
-include specialized proteins
-form a capped end structure
TTAGGG in humans
telomere functions
- protect ends of chromosome from nucleases
- allow cells to distinguish chromosome ends from broken DNA
- prevent chromosomes from fusing with each other
- attachment to nuclear scaffold
problem with telomeres
when chromosomes are replicated in most cells, the telomeres get progressively shorter
What is the end-replication problem?
the shortening of DNA molecules with each cell division
DNA polymerase
an enzyme that replicates DNA strands
DNA polymerase steps
- DNA polymerase needs and RNA primer to get started
- builds in a 5’ to 3’ direction to make new DNA strand
- RNA primer is removed, leaving small overhang
- overhang folds back to form a loop (safer from nucleases)
- every time DNA is replicated it gets a bit shorter - eventually this would be a problem
each round of DNA replication leaves 50-200 bp DNA _______ at the 3’ end
unreplicated
cells with telomeres that are 10-12 kb in length (average) divide
50-60 X
cellular senescence is triggered when?
when telomeres are about 4-6kb long
telomerase
solution to the problems
an RNA containing enzyme that adds more nucleotides to the 3’ end of the telomere DNA strands
Steps of telomerase
- telomerase RNA binds to complementary sequence
- nucleotides added to DNA 3’ terminus (elongation)
- telomerase slides over and its RNA binds to another complementary sequence (translocation)
- more nts added to DNA 3’end (elongations
- other strand filled in using DNA polymerase
the steady loss of telomeres results in a limited life-span for most cells
- in culture, most of our cells cycle a set number of times, them die
- same seems to happen in eukaryotic organisms
- due to lack of telomerase enzyme in our cells
telomerase is not present in all cells: present in:
- many tumor cells-unlimited divisions
- one celled organisms- unlimited divisions
- primordial germ cells - unlimited divisions
- tissue stem cells
telomerase is absent in ___
cultured cells from normal tissue - 50 divisions
what happened with telomerase was experimentally added to normal cells?
more cycles observed
some factors in cell aging:
telomere shortening
accumulated errors
chronic risk exposures such as oxidants, UV
glycation- sugar binding DNA, proteins, lipids
Could loss of telomeres cause the aging process?
- yes but there are other factors too
- loss of telomeres certainly provides a maximal limit to the number of cell divisions
could we provide telomerase therapy to restore telomere length ?
- many cancer cells have reactivated their telomerase
- some anticancer therapies are directed at inhibiting telomerase
- if you think you could extend life by adding telomerase, you could increase the risk of cancer
Dolly
-1996
-1st cloned mammal from adult cell
-took nucleus from the udder of an adult ewe, and transplanted it into a de-nucleated embryo
-died at age 6 (most sheep live till 12)
dolly’s telomeres were 20% shorter than normal sheep by age 3, she started developing serious arthritis at age 5, premature aging occurred
genome
the entire DNA content of an organism / cell
Types of DNA sequences
- highly repeated sequences
- moderately repeated sequences
- non-repeated, single copy sequences
Highly repeated sequences
> 100,000 copies/genome;
moderately repeated DNA
- 20-80% of genomes
- few copies to ten of thousand of copies/genome
- some sequences code for proteins needed in large quantities (e.g ribosomal proteins)
- most do no code for any protein
(diagram. red denotes regions rich in moderately repetitive sequence son a chromosome)
Non-repeated DNA
in humans only about 2% of the genome codes for proteins!
blue denotes genes encoding proteins
