5 Chromosomes, the Cell Cycle, and Intro to its regulation Flashcards
Define chromatin
In eukaryotic cells, chromosomal DNA forms a complex with RNA and proteins
Describe the structure of chromatin
The proteins in chromatin are of 2 main types:
- basic (mainly histones)
- and acidic
Chromatin is also associated with phospholipids, enzymes and other molecules
Describe histones
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
Describe how chromatin is packed into bead-like structures (and how chromosomes are formed)
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
Describe the appearance of chromatin in Interphase
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
How and why do cells grow and proliferate?
Cells can
- increase in cell mass
- increase in cell number
Cells grow because:
- foetal development
- growth
- repair
- cell replacement
- reproduction
Describe tissues and cell proliferation
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
Define The cell cycle
The cell cycle is the process where cell materials duplicates and divide, resulting in 2 daughter cells
List the different stages of the cell cycle
Interphase
- G1, S, G2
- M phase (mitosis + cytokinesis)
Describe the interphase stage of the cell cycle
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
Describe the M phase of the cells cycle
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
Describe regulation of the cell cycle
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
Describe Cyclins and Cyclin-dependent Kinases (CDK’s)
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
Describe the regulation of cell cycle progression by CDK-cyclin complex
- 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
Which CDK inactivation control mitotic exit
CDK 1 inactivation
Describe the different cell cycle checkpoints
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
Describe what happens if a checkpoint fails
This can lead to complications like
- Cancer - a disease of uncontrolled cell proliferation
Describe a proto-oncogene
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
Describe inhibitors of Cyclin-CDK complexes
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
Describe which type of tissue cancer can only arise from
Cancer can only arise from cells with proliferative potential
- e.g. epithelium of the skin, GI tract, bone marrow cells
- Labile cells
Define meiosis
Meiosis is a process of cell division for reducing the somatic quantity of DNA (2c) to that found in sex cells or gametes (1c)
Describe where meiosis occurs
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
Describe meiosis
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
List the stages of meiosis 1
Prophase I (5 stages)
Metaphase I
Anaphase I
Telophase I
Describe prophase I (and name the different substages)
Recombination and pairing occur during prophase I of the first meiotic division
Prophase I is divided into 5 stages:
- Leptotene
- Zygotene
- Pachytene
- Diplotene
- Diakinesis
Describe the first stage of Prophase I (L)
Leptotene
- Chromatin condenses to form chromosomes that are not yet split into sister chromatids
- Along their length, chromomeres are visible
Describe the second stage of Prophase I (Z)
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
Describe the third stage of Prophase I (P)
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
Describe the fourth stage of Prophase I (Dip)
Diplotene
- Chromatids are held together by chiasmata as well as by the centromeres
Describe the fifth/last stage of Prophase I (Dia)
Diakinesis
- chiasmata appear to move towards the ends of chromatids (terminalisation)
Describe metaphase I
Each bivalent has 2 centromeres, and these arrange themselves by chance on opposite sides of the metaphase plate
Describe the genetic variation that occurs at Anaphase I
The impact of independent assortment of chromosomes
chance of bivalents arranging themselves along the metaphase plate
Describe anaphase I
Chromosomes move to opposite poles of the cell
- Each pole has a mixture of maternal and paternal chromosomes
(a source of genetic variation)
Describe telophase I
Each daughter cell has half the diploid number of chromosomes
- nuclear envelope may reassemble before prophase II
Describe the stages of meiosis II
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
Describe the important times genetic variation occurs during meiosis
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
Describe numerical chromosomal abnormalities
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)
Describe structural chromosomal abnormalities
A structural abnormality means the chromosome’s structure has been altered in one of several ways
