Chromosome Segregation

Question 1

what holds sister chromatids together?

Answer 1

cohesin
lots of it near centomere - main attachment site
some along the arms

holds chromatids together and resists microtubules from pulling them apart

Question 2

how does the cell know when all chromosomes are attached to BOTH poles?

Answer 2

chromosomes that are not properly attached to both send out WAIT signals
prevent start of anaphase

WAIT signals also sent out when both kinetochore of one chromosome is attached to same pole

Question 3

when is cohesin complex destroyed?

Answer 3

when all cbromosomes are attached properly to both poles
MTs can then pull chromatid apart from sister
destroyed between meta/anaphase in meiosis II

Question 4

cohesin structure?

Answer 4

4 subunits
form ring structure
embrace DNA after DNA replication (after chromosome becomes 2 chromatids
subunit Scc1 is destroyed by specific protease

Question 5

mitosis vs meiosis

Answer 5

mitosis:
1 diploid cell divides once => 2 diploid cells

meiosis:
i diploid cell divides twice => 4 haploid gametes

Question 6

homologous chromosomes vs sister chromatids

Answer 6

homologous chromosomes:
chromosomes exist in homologous pairs, not identical, 1 inherited from each parent

sister chromatids:
chromosome after DNA replication is made up of two IDENTICAL sister chromatids held together by cohesin

Question 7

chromosome assortment in mitosis?

Answer 7

in mitosis - homologous chromosomes ignore their partner and behave independently
sister chromatids separated - 1 into each daughter
then replicate during interphase (S phase) to get back to 2 sister chromatids

means mother and daughters are all genetically identical

Question 8

meiosis chromosome assortment?

Answer 8

Meiosis I:
- homologous chromosomes pair with each other
-crossover + recombination occurs between them
-then each homologous chromosome from a pair separate into different daughters
gives 2 haploid daughters

sister kinetochores attach to SAME poles

meiosis II:
no DNA replication before meiosis II
- separate sister chromatids similarly to in mitosis
gives 4 haploid cells

sister kinetochores attach to DIFFERENT poles

fertilisation restores diploid state in zygote

Question 9

meiosis sources of genetic diversity?:

Answer 9

1. segregation of homologous chromosomes
   (each pair of homologous chromosomes separates independently from other pairs so maternal and paternal inherited DNA mix in daughters - many different possible combinations of maternal/paternal chromosomes in gametes generates large number of possible gamete chromsome arrangements)
2. recombination between homologous chromosomes before meiosis I

Question 10

why is recombination needed?

Answer 10

if two genes are on the same chromosome:
one gene has a good mutation
another has a bad one
good A
bad B

other chromosome has:
Bad A
good B

if there was not recombination the good alleles would not be able to separate from the bad allele and have both good A and B on the same chromosome

recombination allows good A and good B to get onto the same chromosome

Question 11

prophase I:

Answer 11

aim to recombine homologous chromosome
all 4 chromatids involved in recombination
one chromatid on one homologous chromosome can interact with either chromatid on the other

Synaptonemal complex facilitates recombination
ladder like structure stabilises the pair of chromosomes at site of recombination
recombination nodule in the middle

stages of prophase I:
-Leptotene
-Zygotene
-Pachytene: all 3 of these stages have the SC
-Diplotene: after recombination - SC has disassembled
Diakinesis: chromosomes condense before segregation

then nuclear membrane breaks down and chromosomes are segregated

Question 12

order of meiosis I stages:

Answer 12

-prophase I (recombination)
-metaphase I (lining up)
-Anaphase I (separation of homologous chromosomes)

Question 13

chiasmata importance?:

Answer 13

chiasmata (where recombination has occurred) between chromatids hold homologous chromosomes together

cohesins holds sister chromatids within chromosomes togehter and so pulling by MTs won’t separate homologues

so cohesin is destroyed at chromosome arms in meiosis I but is protected at the centromeres
anaphase I can start after this non-centromeric cohesin is gone
now that sister chromatid pair has no connection to the other and can slide apart

in mitosis ALL cohesin is destroyed before anaphase

Question 14

Meiosis I vs Meiosis II

Answer 14

sister kinetochores attach to:
same pole (I)
different pole (II)

cohesin at centromeres is:
protected (I)
destroyed (II)

Question 15

what happens if chiasma is lost in meiosis I?:

Answer 15

without chiasma - no connection between homologues
will behave independently
50:50 chance they segregate into same daughter (mis-segregate)

similar situation if chiasma is very close to telomeres
homologues rely on small amount of cohesin at end of arms to hold pair together
so physical connection is easier to lose between them before they have connected to poles correctly

Question 16

when is centromeric cohesin destroyed?

Answer 16

anaphase II

Question 17

consequences of centromeric cohesin being destroyed too in meiosis I?:

Answer 17

if centromeric cohesin is destroyed too after chromosomes have attached to different poles:
they segredate fine during the first division as they were already properly connected to poles

BUT now the sisters are no longer connected before attaching to poles in both products of meiosis I
so will segregate independently and randomly
leads to 50;50 chance of mis-segregation in each daughter (and overall)

leads to ANEUPLOIDY (monosomy/trisomy depending on if gamete has received BOTH or NEITHER

Question 18

Human aneuploidy:

Answer 18

Down’s syndrome (trisomy 21)

Trisomy 13, trisomy 18

turner syndrome (XO - monosomy of X chromosome)

kleinfelter syndrome (XXY - trisomy of X)

Question 19

why is aneuploidy bad?

Answer 19

50% increase or decrease of gene dosage - cells very sensitive to gene dosage and so altering it can be fatal

most aneuploidy is FATAL

however chromosome 21 is very small - so trisomy 21 is survivable/viable but still has deleterious effects(down’s syndrome)

Question 20

How to tell which meiotic stage aneuploidy arose from?

Answer 20

Meiosis I failure:
end up with 2 homologues in same meiotic product
end up with 2 homologous chromosomes in the same gamete
failure to separate homologues = aneuploid came from meiosis I

Meiosis II failure:
end up with two sisters in one gamete
failure to separate sister chromatids = aneuploid came from meiosis II

Question 21

since recombination creates mosaic chromosomes with sections of both homologues in each - how can you tell if a pair is homologues or sisters?:

Answer 21

look at centromeres
no recombination here
so if centromeres are identical= sister chromatids

Question 22

how can differences in recombination affect chromosome mis-segregation?

Answer 22

no recombination:
-no connection between homologues
-segregate independently in meiosis I
=> more meosis I mis-segregation

single recombination near telomere:
-easier for chiasma to come undone
-homologues can lose connection more easily
-segregate independently
=> more meiosis I mis-segregation

recombination near centromere:
-more likely for centromeric cohesin to be destroyed? i think?
-since already connected to poles - meiosis I segregates normally
-then chromatids segregate independently in meiosis II
=> more meiosis II mos-segregation

Question 23

reason for maternal age effects on aneuploidy rates?

Answer 23

in spermatogenesis:
meiosis starts happening at puberty
happens continuously - new gametes constantly produced

in oogenesis:
meiosis I occurs ONLY BEFORE birth
then arrests
then starts again in puberty - one oocyte at a time during ovulation
arrests in metaphase II
fertilisation triggers second resumption of meiosis
NO NEW MEIOSIS I HAPPENS AFTER BIRTH OF FEMALE

this very long meiotic pause is to blame
recombination is completed before birth
then chromosomes are not segregated until ovulation
the longer the arrest the greater the probability of mis-segregation
due to “cohesin-fatigue hypothesis”

Question 24

cohesin fatigue hypothesis?

Answer 24

cohesin is established only in S phase
IF this is also assumed true for human oocytes
same molecules of cohesin have to stay on chromosome for decades
accidentally destroyed - no way of restoring it as oocyte no longer in S phase and will not re-enter it