DNA Replication Errors & Errors In Mitosis

Question 1

What is aneuploidy? Give an example of aneuploidy and the disease it results in.

Answer 1

Error in cell division that results in the daughter cells having the wrong number of chromosomes.

Trisomy of chromosome 21 - Down’s syndrome

Question 2

Why does aneuploidy of sex chromosomes have less adverse effects than with autosomal aneuploidy?

Answer 2

There is variation in the number of X and Y chromosomes between males and females anyway

Question 3

What can the effect of trisomy in the sex chromosomes result in?

Answer 3

Infertility

Question 4

What can cause aneuploidy?

Answer 4

Anaphase lag

Non disjunction

Question 5

What is nondisjunction? What cells does it result in? Can it happen in mitosis or meiosis?

Answer 5

Where both copies of a chromosome go into 1 daughter cell

Results in cells with one copy too many and 1 copy too few

Both mitosis and meiosis

Question 6

Which chromosomes are used in chromosome analysis?

Answer 6

Metaphase chromosomes from an actively dividing cell

Question 7

A karyotype can be displayed in which two ways?

Answer 7

A visual spread of chromosomes grouped by size/shape

Written notation

Question 8

What would the karyotype for a normal male be?

Answer 8

46,XY

Question 9

What would the karyotype for a Down’s syndrome female be?

Answer 9

47,XX,+21

Question 10

If non disjunction happens in the first post-zygotic division which sort of karyotype will be produced?

Answer 10

Non-mosaic karyotype

Question 11

Monosomy is only viable for life in which case?

Answer 11

A female with one X chromosome

Question 12

If non disjunction occurs after the first post zygotic division which sort of karyotype will be produced?

Answer 12

A mosaic karyotype will be produced

Question 13

What is mosaicism?

Answer 13

The presence of two or more cell lines in an individual

Question 14

If non disjunction happens in meiosis 1, what will be the effect on the four daughter cells?

Answer 14

50% trisomy
50% monosomy

(All affected)

Question 15

If non disjunction happens in meiosis 2 what will be the effect?

Answer 15

50% normal
25% trisomy
25% monosomy

Question 16

What is more important in contributing to genetic diversity; random assortment or crossing over?

Answer 16

Both equally important

Question 17

What is the difference between anaphase lag and nondisjunction?

Answer 17

Anaphase lag results in 1 normal cell and 1 monosomic cell

Nondisjunction produces a trisomic and monosomic cell

Question 18

What is a Robertsonian translocation?

Answer 18

Happens between two acrocentric chromosomes, results in the breaking of each chromosome at the centromere and the two longer arms forming a new chromosome and the two shorter arms forming a chromosome (which is usually lost)

Question 19

DNA damage can be separated into which 2 categories?

Answer 19

Endogenous

Exogenous

Question 20

Give 4 examples of exogenous causes of DNA damage.

Answer 20

Ionising radiation
Alkylating agents
UV light
Anti-cancer agents

Question 21

Give two examples of endogenous causes of DNA damage?

Answer 21

Dna replication errors

Free radicals

Question 22

What checkpoints exist to repair DNA damage? What happens at these checkpoints to allow time for repair?

Answer 22

G1 checkpoint
G2 checkpoint
Checkpoint in mitosis

Temporary cell cycle arrest

Question 23

If dna damage is too high or persists what two mechanisms are used to prevent the DNA damage resulting in cancer?

Answer 23

Apoptosis

Senescence = permanent cell cycle arrest

Question 24

By which 2 methods can DNA DSBs be repaired?

Answer 24

Homologous-directed repair

Non homologous end joining

Question 25

What does non-homologous end joining involve?

Answer 25

KU70/KU80 protect ends Proteins recruited Ligation of two broken ends back together

Question 26

What are two types of homology directed repair?

Answer 26

Single strand annealing Synthesis dependent strand annealing (SDSA)

Question 27

What happens in the single strand annealing method of repairing DNA DSBs?

Answer 27

Break repaired - leads to deletions

Question 28

What happens in the SDSA method of repairing DNA DSBs?

Answer 28

Uses identical DNA molecule to rebuild/repair itself | Uses DNA polymerase

Question 29

What is meant by intra-tumour heterogeneity? What does it result in?

Answer 29

Different sub-clones within the same tumour Tumour evolution and drug resistance

Question 30

What is often seen when using chemotherapy drugs on a heterogenous tumour? What are the disadvantages of using chemotherapy on a tumour with regards to tumour evolution?

Answer 30

Initial shrinking of the tumour and then further expansion of resistant sub clones of the tumour (comes back worse and is now resistant) The chemotherapy itself can cause mutations, some of which could give advantageous resistance mutations -->further evolution

Question 31

How does cisplatin work as a cancer drug?

Answer 31

Causes dna damage in cancer cells by forming cross-links

Question 32

What is the main consequence of the shortening of telomeres?

Answer 32

Cell death/ageing

Question 33

How is the progressive shortening of chromosomes and telomeres prevented?

Answer 33

Telomerase aids in the replication of the ends of chromosomes and prevents chromosome degradation

Question 34

What is a problem that can arise from the 'non homologous end joining' repair of DSBs?

Answer 34

More than 1 DSB close together may result in the wrong ends being joined together

Question 35

What is chromosomal translocation? What can it result in?

Answer 35

Rearrangement of parts between non homologous chromosomes Gene fusion

Question 36

What is chromosome inversion? How does it occur?

Answer 36

Where a segment of a chromosome is reversed end to end A single chromosome undergoes breakage and arrangement within itself

Question 37

At which point of the cell cycle do non dividing cells enter G0?

Answer 37

At a point in G1 called the restriction point.

Question 38

Which organelle is important in ensuring the accuracy of chromosome segregation?

Answer 38

The mitotic spindle

Question 39

What is the structure of the mitotic spindle?

Answer 39

Part of the cell cytoskeleton - made of microtubules

Question 40

What is the function of a centrosome? How many of them are in each cell? Where do they travel in mitosis?

Answer 40

Organises the microtubules in the cell cycle 2 in each cell To opposite poles of the cell

Question 41

The mitotic spindle is a proven target for successful treatment of...

Answer 41

Cancer

Question 42

What is the chromosome status of most cancer cells?

Answer 42

Most cancer cells are aneuploid and show chromosome instability

Question 43

Most cancer cells are aneuploidy and have increased copies of certain chromosomes, this results in increased expression of...

Answer 43

Oncogenes

Question 44

What is the result of an increased number of centrosomes? In which cells are amplified chromosomes normally found?

Answer 44

Multipolar spindles are formed that promote chromosome instability Cancer cells

Question 45

If cancer cells often show amplified centrosomes, how are only two cells still produced in cell division? How can these mechanisms be exploited in cancer treatment?

Answer 45

Cancer cells have mechanisms to cluster these amplified chromosomes to produce two cells with aneuploidy Inhibiting centrosome clustering in cancer cells ---> in cell death and a possible cancer treatment with less side effects as it is specific to cancer cells

Question 46

In which stage of mitosis is there a cell cycle checkpoint? How is this checkpoint 'passed'?

Answer 46

Metaphase Checkpoint passed if all chromosomes are attached to the mitotic spindle

Question 47

What is cohesin?

Answer 47

The molecular glue that holds sister chromatids together, made from 4 proteins and makes a ring structure with dna

Question 48

What is the loading and offloading of cohesin regulated by?

Answer 48

Cohesin control proteins