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1

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

2

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

3

diploid number

2n
number of chromosomes per somatic (body) cell

4

Haploid number

n
number of chromosomes in gametes
-humans 2n=46 (22 autosomes and 2 sex chromosomes)
-mouse 2n=40
-drosophila 2n=8

5

aneuploidy

abnormal number of chromosomes

6

examples of aneuploidy?

trisomy= one extra chromosome
monosomy=missing chromosome

7

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

8

Chromosomes are NOT indestructible!

-can be broken and when repaired they may get scrambled.

9

translocations

movement to new chromosome

10

inversions

portion of chromosome is flipped

11

deletions

section of DNA excised

12

insertions

section of DNA inserted

13

translocations are the transfer of a piece of one chromosome to a _____________ chromosome

nonhomologous

14

translocations can result in change in phenotype by:

1. breaking a gene
2. moving gene to a region where it can be controlled by another regulatory sequence
3. creating hybrid gene
(can elongate one side of chromosome)

15

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

16

Translocation distinguishes human and ape karyotypes

-apes=48 chromosomes
-humans = 46 chromosomes
-genes in humans and chimps differ by

17

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

18

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

19

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

20

problem with telomeres

when chromosomes are replicated in most cells, the telomeres get progressively shorter

21

What is the end-replication problem?

the shortening of DNA molecules with each cell division

22

DNA polymerase

an enzyme that replicates DNA strands

23

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

24

each round of DNA replication leaves 50-200 bp DNA _______ at the 3' end

unreplicated

25

cells with telomeres that are 10-12 kb in length (average) divide

50-60 X

26

cellular senescence is triggered when?

when telomeres are about 4-6kb long

27

telomerase

solution to the problems
an RNA containing enzyme that adds more nucleotides to the 3' end of the telomere DNA strands

28

Steps of telomerase

1. telomerase RNA binds to complementary sequence
2. nucleotides added to DNA 3' terminus (elongation)
3. telomerase slides over and its RNA binds to another complementary sequence (translocation)
4. more nts added to DNA 3'end (elongations
5. other strand filled in using DNA polymerase

29

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

30

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