5 Chromosomes, the Cell Cycle, and Intro to its regulation

Question 1

Define chromatin

Answer 1

In eukaryotic cells, chromosomal DNA forms a complex with RNA and proteins

Question 2

Describe the structure of chromatin

Answer 2

The proteins in chromatin are of 2 main types:

• basic (mainly histones)
• and acidic

Chromatin is also associated with phospholipids, enzymes and other molecules

Question 3

Describe histones

Answer 3

Histones are rich in amino acids

• Core histones are H2A, H2B, H3, H4
• 2 of each forms the core histone octamer
• DNA winds twice around it
• Linker histones are H1 and H5, which hold the DNA to the histone core

These are important in compacting DNA and in chromatin regulation

Question 4

Describe how chromatin is packed into bead-like structures (and how chromosomes are formed)

Answer 4

Chromatin is packed into bead-like structures called nucleosomes
- each nucleosome has 2 loops of DNA double helix warped around a cluster of 8 histones

Chromosomes form by the supercoiling and condensation of chromatin

Genes are specialised functional sites arranged along the chromosomes

Question 5

Describe the appearance of chromatin in Interphase

Answer 5

In interphase nuclei, chromatin appears in 2 main forms:

Heterochromatin
- more condensed and densely stained
- tends to be found near nuclear envelope
- represents genes which are switched off (not expressed)
- Two types:
> constitutive
> facultative (sometimes on)

Euchromatin

• less condensed and lightly staining
• more central location
• represents genes which are switched on

Question 6

How and why do cells grow and proliferate?

Answer 6

Cells can

• increase in cell mass
• increase in cell number

Cells grow because:

• foetal development
• growth
• repair
• cell replacement
• reproduction

Question 7

Describe tissues and cell proliferation

Answer 7

Tissues of the body can be divided into 3 main groups according to their rates of turnover:

Continuously renewing
- epidermis of skin, intestinal epithelium

Conditionally renewing
- liver, kidney, endocrine glands

Static or non-proliferative
- cardiac, nerve cells

Question 8

Define The cell cycle

Answer 8

The cell cycle is the process where cell materials duplicates and divide, resulting in 2 daughter cells

Question 9

List the different stages of the cell cycle

Answer 9

Interphase

• G1, S, G2
• M phase (mitosis + cytokinesis)

Question 10

Describe the interphase stage of the cell cycle

Answer 10

Interphase:

G1 (gap/growth 1)
- cell growth, 6-12h

S phase (synthesis)
- DNA replication 6-8h

G2 (gap/growth 2)
- preparation for cell division 3-4h

Question 11

Describe the M phase of the cells cycle

Answer 11

Mitosis and cytokinesis
- the formation of 2 identical daughter cells

Mitosis results in

• nuclear division (karyokinesis)
• cytoplasmic division (cytokinesis)

The nuclear division of mitosis has several stages:

• prophase
• pro-metaphase
• metaphase
• anaphase
• telophase

Question 12

Describe regulation of the cell cycle

Answer 12

Cyclins and Cyclin-dependent Kinases (CDKs)

• they are regulatory molecules
• these proteins coordinate the Cell’s entry into the next phase of the cell cycle

Question 13

Describe Cyclins and Cyclin-dependent Kinases (CDK’s)

Answer 13

CDKs become activated upon binding with cyclin

• activated CDKs then cause phosphorylation to activate/inactivate target proteins
• these activated proteins coordinate cell’s entry into the next phase of the cell cycle

Question 14

Describe the regulation of cell cycle progression by CDK-cyclin complex

Answer 14

• Cyclins are made and degraded cyclically
• They activate CDK’s
• So that the cell cycle cannot go backwards
• different CDK-cyclin complexes control different stages of the cell cycle
• relative concentration levels of the different CDK-cyclin complexes fluctuate, to trigger the next stage of the cell cycle

Question 15

Which CDK inactivation control mitotic exit

Answer 15

CDK 1 inactivation

Question 16

Describe the different cell cycle checkpoints

Answer 16

G1 checkpoints

• check if there are plenty of nutrients
• check at end of G1
• if ok - enter the S phase
• or pause/enter G0

G2 checkpoints

• check if DNA replicated correctly and intact
• if ok, enter mitosis

Mitotic checkpoint

• check if chromosomes are properly aligned
• M-cyclin degradation, CDK inactivation, and anaphase-cytokinesis

Question 17

Describe what happens if a checkpoint fails

Answer 17

This can lead to complications like

- Cancer - a disease of uncontrolled cell proliferation

Question 18

Describe a proto-oncogene

Answer 18

Proto-oncogene

• A normal gene which, when altered by mutation, becomes an oncogene that can contribute to cancer
• Some proto-oncogenes provide signals that lead to cell division

Question 19

Describe inhibitors of Cyclin-CDK complexes

Answer 19

Two families of genes prevent the progression of the cell cycle
- e.g. CIP/KIP family halt the cell cycle in G1, by binding and inactivating a complex of Cyclin-CDK
- These proteins are of medical interest - as they arrest the cell cycle
- could be anticancer agents
aka tumour suppressors

Question 20

Describe which type of tissue cancer can only arise from

Answer 20

Cancer can only arise from cells with proliferative potential

• e.g. epithelium of the skin, GI tract, bone marrow cells
• Labile cells

Question 21

Define meiosis

Answer 21

Meiosis is a process of cell division for reducing the somatic quantity of DNA (2c) to that found in sex cells or gametes (1c)

Question 22

Describe where meiosis occurs

Answer 22

The process occurs in:

• the ovaries (oogenesis)
• the testes (spermatogenesis)

When male (1c) and female (1c) gametes fuse to form the zygotes, the 2c quantity of DNA is restored

Question 23

Describe meiosis

Answer 23

Since DNA is duplicated in the S phase prior to cell division, we begin with 4c quantity of DNA
- therefore, there must be 2 separate reduction division to achieve the 1c amount in gametes

These are called 1st and 2nd reduction division or meiosis 1 and meiosis 2:

• Meiosis 1 reduces 4c to 2c
• Meiosis 2 reduces 2c to 1c

Question 24

List the stages of meiosis 1

Answer 24

Prophase I (5 stages)
Metaphase I
Anaphase I
Telophase I

Question 25

Describe prophase I (and name the different substages)

Answer 25

Recombination and pairing occur during prophase I of the first meiotic division Prophase I is divided into 5 stages: - Leptotene - Zygotene - Pachytene - Diplotene - Diakinesis

Question 26

Describe the first stage of Prophase I (L)

Answer 26

Leptotene - Chromatin condenses to form chromosomes that are not yet split into sister chromatids - Along their length, chromomeres are visible

Question 27

Describe the second stage of Prophase I (Z)

Answer 27

Zygotene - homologous chromosomes (maternal-paternal) pair together to form bivalents - Chromosomes are now split into sister chromatids and local sites of alignment (synapsis) develop between sister chromatids of homologous pairs

Question 28

Describe the third stage of Prophase I (P)

Answer 28

Pachytene - synapsis is completed and 'crossing over' occurs > chiasmata formation - At chiasmata, genetic information is exchanged between homologous pairs - This is more likely to happen between long stretches of chromatid arms than short ones

Question 29

Describe the fourth stage of Prophase I (Dip)

Answer 29

Diplotene | - Chromatids are held together by chiasmata as well as by the centromeres

Question 30

Describe the fifth/last stage of Prophase I (Dia)

Answer 30

Diakinesis | - chiasmata appear to move towards the ends of chromatids (terminalisation)

Question 31

Describe metaphase I

Answer 31

Each bivalent has 2 centromeres, and these arrange themselves by chance on opposite sides of the metaphase plate

Question 32

Describe the genetic variation that occurs at Anaphase I

Answer 32

The impact of independent assortment of chromosomes | chance of bivalents arranging themselves along the metaphase plate

Question 33

Describe anaphase I

Answer 33

Chromosomes move to opposite poles of the cell - Each pole has a mixture of maternal and paternal chromosomes (a source of genetic variation)

Question 34

Describe telophase I

Answer 34

Each daughter cell has half the diploid number of chromosomes - nuclear envelope may reassemble before prophase II

Question 35

Describe the stages of meiosis II

Answer 35

These are morphologically similar to those seen in mitosis - centromeres are now split at the kinetochores and sister chromatids move to opposite poles - At the end of the 3 divisions (meiosis I and II), potentially 4 gametes (tetrad of haploid cells) are formed

Question 36

Describe the important times genetic variation occurs during meiosis

Answer 36

Pachytene of prophase I - genetic information is exchanged between homologous pairs of chromosomes at chiasmata Anaphase I - each pole has a mixture of maternal and paternal assortment, resulting in independent assortment Fertilisation - by chance

Question 37

Describe numerical chromosomal abnormalities

Answer 37

A numerical abnormality means an individual is either: - Missing one of the chromosomes from a pair (trisomy) - Or has more than 2 chromosomes - One extra is trisomy 2 extra is tetrasomy e.g. most common is trisomy (Down syndrome)

Question 38

Describe structural chromosomal abnormalities

Answer 38

A structural abnormality means the chromosome's structure has been altered in one of several ways