cell cycle

introduction

• modern cell theory states that all new cells are derived from pre-existing cells through cell division

  • cell division involves both nuclear division and cytokinesis

• two types of nuclear division

  1. mitosis: nuclear division that produces

     • two genetically identical daughter nuclei → same DNA

     • each containing the same number of chromosomes as the parent nucleus

  2. meiosis: nuclear division that produces

     • four daughter nuclei which are not genetically identical

     • each containing half the number of chromosomes as the parent nucleus

  • meiosis is also known as reduction division, since the number of chromosomes in the cell is halved (haploid)

• two types of cells are obtained from cell division:

  1. somatic cells: all body cells except the reproductive cells → mitosis gives rise to somatic cells

  2. gametes: reproductive cells, such as sperms and eggs → meiosis gives rise to gametes

chromosome structure

• chromatin which is highly condensed to become a distinct visible structure

• observed in a dividing cell → a cell undergoing mitosis or meiosis

sister chromatids

• each replicated chromosome appears as a double arm structure which consists of two sister chromatids joined together

• each chromatid is made up of one DNA molecule

• sister chromatids are genetically identical (same nucleotide sequence) as the DNA is replicated during S phase of interphase

centromere

the region at which the two sister chromatids of a single replicated chromosome are joined

spindle fibre/mitotic fibre

• structure that consists of fibres made up of microtubules (proteins synthesised by ribosomes) and associated proteins (tubulin proteins)

• able to lengthen or shorten → by adding or removing the tubulin proteins

centrosome

• microtubule organizing centre (MTOC) in animal cells

• made up of a pair of centrioles

  • role of centrioles during mitosis (function)

    1. the centrioles organise the spindle fibres

    2. to separate sister chromatids during anaphase of mitosis

    3. each pole of the cell has a pair of centrioles

kinetochore

• disc-shaped protein structure which binds to the chromatids at the centromere

• location where spindle fibres (microtubules) attach during nuclear division

• the spindle fibres extend from the kinetochores to the poles to the centrosome

cell cycle

• for cell division to occur, cells undergo a sequence of events, known as the cell cycle

cell cycle refers to the period from which the cell is formed by cell division (i.e. start of G1 phase) to the point that the cell itself divides (i.e., end of cytokinesis)

• cell cycle comprises 3 phases: interphase (majority of the time), mitosis/meiosis (nuclear division), cytokinesis

• the duration of the cell cycle is highly variable

  • e.g.: root tip cells of onion divide once every 20 hours, while epithelial cells in the human intestine divide once every 10 hours

• most types of cells never divide again after they become specialised → exits the cell cycle ⇒ protects integrity of DNA in cell

  • e.g. guard cells in plants and many cells of the mammalian nervous system

interphase

• in this phase, the cell prepares for cell division

• volume of cell increases as DNA is replicated and organelles are synthesised during interphase

• all non-dividing specialised cells (e.g., white blood cell) exit the cell cycle and enter the G0 (resting) phase after the M phase (mitosis) → where they do not proceed further in the cell cycle

interphase comprises 3 subphases

1. G1 (first “gap”) phase

   • occurs after cytokinesis

   • duration is highly variable (lasting from a few hours to months or years)

   • cell grows and synthesizes proteins, enzymes, and RNA

2. S (synthesis) phase

   • replication of DNA occurs → doubles the amount of DNA in the cell

   • one DNA molecule is replicated to form 2 DNA molecules, each DNA consisting of one daughter strand and one parental DNA strand

3. G2 (second “gap”) phase

   • cell continues to grow and synthesize proteins; it includes ribosomal proteins and proteins which make up the spindle fibres

   • formation of new organelles in preparation for cell division

   • centrosome duplicates (each daughter cell has one) in preparation for cell division

mitosis

• comprises of 4 stages: prophase, metaphase, anaphase and telophase (PMAT)

overview

• at G1 phase of interphase:

  • 1 DNA molecule is found in 1 chromosome → before DNA replication

• at S phase of interphase:

  • DNA molecule replicates to form two genetically identical DNA molecules

  • DNA molecules are joined at the centromere to form 1 chromosome

• at prophase of mitosis:

  • the 2 DNA molecules will condense to form a chromosome with two sister chromatids

  • each sister chromatid is one DNA molecule

• at telophase of mitosis and after cytokinesis:

  • sister chromatids are separated into two daughter cells

  • each daughter cell contains 1 chromosome, which is made up of 1 DNA molecule

prophase → mitosis

1. chromosomes become visible due to condensation of chromatin

2. each chromosome consists of two sister chromatids, joined at the centromere [due to DNA replication]

3. the nucleolus disappears → not an organelle/physical structure

4. in animal cells, the centrosomes (duplicated) migrate to opposite poles of the cell

5. spindle fibres extend from each pole towards the equator of the cell

6. nuclear envelope breaks down, due to the nuclear envelope fragmenting into vesicles

metaphase → mitosis

1. spindle fibres attach to the kinetochore at the centromere of the chromosome

2. chromosomes arrange in a single row, at the metaphase
   plate / equator of the cell

anaphase → mitosis

1. the centromere of each chromosome divides, causing the sister chromatids of each chromosome to separate

2. the sister chromatids move to opposite poles of the cell, centromeres first

3. this is due to the shortening of the spindle fibres

4. the cell elongates as non-kinetochore spindle fibres (do not interact with kinetochore proteins on chromosomes) lengthen

telophase → mitosis

1. the sister chromatids reach the respective poles of the cell and become the chromosomes of the daughter cells

2. the chromosomes uncoil and become chromatin → less visible

3. nucleolus in each nucleus reappears

4. nuclear envelope reforms around the chromosomes at each pole, due to the fusion of nuclear membrane vesicles

5. the spindle fibres break down

significance of mitosis

• mitosis maintains genetic stability of an organism or a cell from one generation to the next

  • two daughter cells formed are genetically identical to the parent cell

  • daughter cells have the same number and type of chromosomes as the parent cell

• mitosis occurs during the growth and development of a multicellular organism.

  • e.g. development of a fertilized egg (zygote) into an adult human being

• mitosis occurs during the replacement of cells of worn-out tissues of the body

  • e.g. skin cells are constantly dying and are replaced with new identical cells

• mitosis is the basis of asexual reproduction

  • e.g. vegetative propagation in plants

  • production of offspring that are identical to parents allows a population to rapidly colonise/spread in a habitat

• mitosis occurs during an immune response

  • e.g. proliferation / cloning of activated B lymphocytes and T lymphocytes

how mitosis maintains genetic stability from one generation of cells to the next

1. replication of DNA occurs in the parent cell before mitosis begins

   • amount of DNA is doubled during S phase of interphase and halved after cytokinesis

2. chromosomes are arranged at the equator of the cell during metaphase

3. sister chromatids separate during anaphase and are evenly distributed between the two nuclei during telophase

what would happen if mitosis did not occur properly in a cell?

abnormal number of chromosomes in daughter cells → chromosomal mutation → may lead to cancer

rate of mitosis

• length of cell cycle depends on:

  • type of cell

    • e.g. epithelial cells lining the intestine divide every 8 to 10 hours, however, nerve cells and red blood cells do not divide

  • environmental factors

    • e.g. food, temperature, and oxygen supply

meiosis

• consists of 2 successive nuclear divisions

  • meiosis I → first meiotic division

  • meiosis II → second meiotic division

• each meiotic division is divided into 4 stages: prophase, metaphase, anaphase and telophase

• DNA replication during S phase of interphase (precedes meiosis)

• homologous chromosomes are not normally condensed to form chromosomes during interphase

• after the chromosomes replicate once, the diploid cell divides twice to yield four haploid daughter cells

• meiosis is also known as reduction division, since the number of chromosomes in the cell is halved

ploidy

• refers to the number of sets of chromosomes within the nucleus of a cell

diploid (2n)

• a diploid cell has two sets of chromosomes, one set derived from each parent

• the total number of chromosomes in a diploid cell is represented as 2n

• human somatic cells have a diploid number of 46 chromosomes (2n = 46) ⇒ 23 pairs of chromosomes: 22 pairs of homologous chromosomes plus a pair of sex chromosomes in all human somatic cells

haploid (n)

• haploid cell has only one set of chromosomes

• only one member of each pair of chromosomes is present → either X or Y chromosomes

• the total number of chromosomes in a haploid cell is represented as n

• human gametes (ovum, sperm) are haploid, and they contain 23 chromosomes (n = 23)

homologous chromosomes

• refers to a pair of chromosomes with the following structural features: same arm length and shape, same centromere position, same sequence of genes along the chromosome and same staining pattern (in a karyotype)

• a pair of homologous chromosomes is similar but not genetically identical

• they contain the same number and type of genes (e.g., genes that code for characteristics like eye colour), but they may be of different alleles (e.g. one allele
  codes for blue eyes while the other allele codes for brown eyes)

• inherit one chromosome of each homologous pair from each parent

bivalents

describes homologous chromosomes that pair up during prophase I of meiosis, in a process known as synapsis

non-sister chromatids

• chromatids of a pair of homologous chromosomes

• have the same number and sequence of genes but may carry different alleles

non-sister chromatids should only be used when describing crossing over during prophase I of meiosis, not when describing other processes in mitosis or meiosis

synapsis

• occurs during prophase I of meiosis

• homologous chromosomes pair up (form bivalents) and are physically connected to each other

crossing over

exchange of corresponding sections between chromatids of a pair of homologous chromosomes when they are in synapsis

chiasma/chiasmata (plural)

• x-shaped structure formed between chromatids (non-sister chromatids) of a pair of homologous chromosomes

• the site(s) where corresponding sections of homologous chromosomes break and rejoin (form recombinant chromatids)

• enables exchange of genetic material to occur between homologous chromosomes, in a process known as crossing over ⇒ chromatids are no longer genetically identical

prophase 1 → meiosis

1. chromosomes become visible due to condensation of chromatin

2. homologous chromosomes pair up in a process known as synapsis, and each pair of homologous chromosomes constitutes a bivalent

3. chiasmata may form between chromatids of a pair of homologous chromosomes, and crossing over occurs

4. centrosomes migrate to opposite poles of the cell

5. spindle fibres extend from each pole towards the equator of the cell

6. the nucleolus disappears and nuclear envelope breaks down, due to the nuclear membrane fragmenting into vesicles

metaphase I → meiosis

1. spindle fibres attach to the kinetochore at the centromere of the chromosome

2. the homologous chromosomes arrange in two rows at the metaphase plate / equator of the cell

3. the arrangement of each pair of homologous chromosomes is completely independent of the arrangement of other pairs

anaphase I → meiosis

1. homologous chromosomes separate and move to opposite poles of the cell, centromeres first

2. this is due to the shortening of the spindle fibres

3. the cell elongates as non-kinetochore spindle fibres lengthen

telophase I → meiosis

1. chromosomes reach opposite poles of the cell

2. nucleolus in each nucleus reappears

3. nuclear envelope reforms around each group of chromosomes at each pole, due to the fusion of nuclear membrane vesicles

4. the spindle fibres break down

end of meiosis I

• at the end of meiosis I and after cytokinesis, two daughter cells are formed → each daughter cell possesses haploid number of chromosomes

• the nuclei of the daughter cells (at the end of Meiosis I) may enter interphase (chromosomes uncoil) but DNA replication does not occur → only happens once in both mitosis and meiosis

• in some cells of certain species, there is neither telophase I nor interphase, and the cell passes from anaphase I into prophase II directly ⇒ their chromosomes do not uncoil

• cytokinesis (division of the cytoplasm) usually occurs simultaneously with telophase I, forming two haploid daughter cells

prophase II → meiosis

1. in cells where Telophase I and Interphase occur, the nucleolus disappears, and nuclear envelope breaks down, due to the nuclear membrane fragmenting into vesicles

2. if centrosomes are present, they migrate to opposite poles of the cell

3. the spindle fibres develop at right angles/perpendicular to the spindle axis of meiosis I

metaphase II → meiosis

1. spindle fibres attach to the kinetochore at the centromere of the chromosome

2. chromosomes arrange themselves 90° to the new spindle axis in a single row, at the metaphase plate/equator of the cell

anaphase II → meiosis

1. the centromere of each chromosome divides, causing the chromatids of each chromosome to separate

2. the chromatids move to opposite poles of the cell, centromeres first

3. this is due to the shortening of the spindle fibres

telophase II → meiosis

1. the chromatids reach the opposite poles of the cell and become the chromosomes of the daughter cells

2. the chromosomes uncoil and become chromatin

3. nucleolus in each nucleus reappears

4. nuclear envelope reforms around the chromosomes at each pole, due to the fusion of nuclear membrane vesicles

5. the spindle fibres break down

• at the end of meiosis II and cytokinesis, the parent cell has divided to four daughter cells → each daughter cell possesses a haploid number of chromosomes

significance of meiosis

1. meiosis gives rise to genetic variation between gametes through crossing over of homologous chromosomes and the independent assortment of bivalents

2. meiosis prevents doubling of chromosome numbers upon fusion of gametes

   • in sexually reproducing species, meiosis produces four haploid gametes, which are genetically non-identical

   • each gamete has half the number of chromosomes of the parent cell

   • during fertilization, the nuclei of one male and one female haploid gamete fuse to restore the diploid number (2n) of chromosomes in the zygote

   • if meiosis did not occur, fusion of gametes would result in a doubling in the number of chromosomes for each successive sexually reproduced generation

how meiosis brings about genetic variation:

• crossing over between homologous chromosomes during prophase I → there is an exchange of genetic material between homologous chromosomes

• independent assortment of chromosomes

  • independent arrangement of homologous chromosomes at the equator of the cell during metaphase I and their subsequent separation during anaphase I

  • random arrangement of the non-identical chromatids at the equator during metaphase II, and the subsequent separation of the non-identical chromatids during
    anaphase II [when crossing over occurs in prophase I, the sister chromatids are no longer genetically identical]

• both crossing over and independent assortment of chromosomes will lead to new combination of alleles

• all 4 resultant cells are different from one another → with more pairs of homologous chromosomes, the number of possible combinations of alleles becomes enormous

  • a human, with 22 homologous pairs of chromosomes + 1 pair of sex chromosomes, has a potential of 2²³ = 8,388,608 different combinations of alleles

genetic variation

genetic variation: differences in the DNA sequences between individuals of a species

• essential for evolution by providing a varied population of individuals

• allows natural selection of individuals best adapted to survive under certain environmental condition, ensuring that the species would be able to survive even when environmental conditions change

• meiosis, random fertilisation of gametes and mutation can lead to genetic variation

random fertilisation of gametes also contributes to genetic variation of an individual ⇒ fusion of a male and a female gamete is due to chance

differences between mitosis and meiosis

mitosis	meiosis
DNA replicates once, and nucleus divides once	DNA replicates once, but there are two successive nuclear divisions
homologous chromosomes do not pair up during prophase	homologous chromosomes associate to form bivalents in prophase I
chiasmata are not formed	chiasmata likely to form
crossing over does not occur	crossing over likely to occur
chromosomes form a single row at the equator of the cell during metaphase	homologous chromosomes form two rows at the equator of the cell during metaphase I
homologous chromosomes are not separated during anaphase	homologous chromosomes are separated during anaphase I
two daughter cells are formed	four haploid daughter cells are formed
daughter cells have the same number of chromosomes as the parent cell	daughter cells have only half the number of chromosomes found in the parent cell
daughter cells are genetically to parent cell in absence of mutation	daughter cells are genetically different from parent cell

cytokinesis

cytokinesis: cytoplasmic division of a cell between the two nuclei, bringing about the separation into two daughter cells

• cytokinesis and mitosis/meiosis are separate processes

  • cytokinesis accompanies mitosis, usually beginning of telophase

cytokinesis in animal cells

• a contractile ring (protein), made of actin filaments, surrounds the dividing cell

  • as the contractile ring contracts, it pulls the cell surface membrane inwards to form a cleavage furrow

  • cleavage furrow deepens and eventually separates to form 2 daughter cells

cytokinesis in plant cells

• a series of Golgi vesicles appear in the middle of the parent cell

  • the contents of the Golgi vesicles are used to form the cell walls that separates the daughter cells

  • the membranes of the Golgi vesicles (phospholipid bilayer) form the new cell surface membrane

• the Golgi vesicles fuse to form the cell plate, which grows outwards

  • the cell plate eventually fuses with the parent cell wall and cell surface membrane, separating the two daughter cells