Source: Chapters 8–9, University of Central Florida
Tags: centromere, kinetochore, sister chromatids, homologous chromosomes, cell cycle phases, G1, S phase, G2, M phase, mitosis, meiosis, cohesin, condensin, anaphase, metaphase checkpoint, ploidy, 4n, Aurora B kinase, spindle assembly checkpoint
Difficulty: Intermediate Prerequisites: Genome Organisation notes (Part 1 of this set), basic cell biology including understanding of DNA as double-stranded.
This section deals with the physical behaviour of chromosomes during the cell cycle, mitosis, and meiosis. You need to understand how chromosomes are structured (centromeres, kinetochores, telomeres), how they duplicate and segregate, and what checkpoints keep the process accurate. The cell cycle phases and what happens during each are heavily tested. If you are unclear on the difference between sister chromatids and homologous chromosomes, sort that out before continuing, because nearly every question in this section depends on it.
Chromosomes attach to the mitotic spindle via kinetochore proteins at the centromere. Sister chromatids are identical copies joined at the centromere from S phase through M phase. The cell cycle alternates between growth (G1, G2), DNA synthesis (S), and division (M), with checkpoints at each transition. Meiosis I and II differ in how microtubules attach and what holds chromatids in tension at the metaphase plate.
Centromere
The specialised chromosomal region where kinetochore proteins attach, linking chromosomes to spindle microtubules during cell division. Think of it as the anchor point that the cell's machinery grabs to pull chromosomes apart.
Kinetochore
A protein complex that assembles on the centromere and directly contacts centromeric DNA (or associated histones). Microtubules attach to kinetochores, not directly to the DNA.
Telomere
The repetitive DNA sequences at the ends of linear chromosomes that protect against degradation and fusion. Not the attachment point for spindle fibres.
Sister chromatids
Two identical copies of a single chromosome, joined at the centromere. They exist from S phase (after DNA replication) through to M phase (until they are separated). They are not the same thing as homologous chromosomes.
Homologous chromosomes
A pair of chromosomes (one from each parent) that carry genes for the same traits at the same loci but may have different alleles. Homologues are not identical copies; sister chromatids are.
Cohesin
A protein complex that holds sister chromatids together from S phase until anaphase. Its cleavage during anaphase allows sister chromatids to separate. During meiosis II, cohesin provides the tension that holds sister chromatids at the metaphase plate.
Condensin
A protein complex that compacts chromosomes during prophase. Condensin is activated (not cleaved) during early stages of mitosis to condense chromatin into visible chromosomes.
G1 phase
The first gap phase: growth and preparation for DNA replication. Chromosomes are unreplicated single molecules of dsDNA.
S phase
The synthesis phase: DNA replication and histone duplication occur. By the end of S phase, each chromosome consists of two sister chromatids.
G2 phase
The second gap phase: growth and preparation for cell division. Chromosomes are fully replicated (sister chromatids joined at centromeres).
M phase
Mitosis and cytokinesis. Chromosomes condense, align, and segregate. Microtubules attach to kinetochores at centromeres (not telomeres).
Karyotype
A visual display of an organism's chromosomes, arranged by size and shape. A karyotype image showing paired structures with visible constrictions shows both homologous chromosomes and sister chromatids.
Aurora B kinase
A kinase that senses tension from microtubule attachment at kinetochores during metaphase. High tension signals correct bipolar attachment.
Spindle assembly checkpoint (metaphase checkpoint)
A checkpoint in late metaphase where kinetochores signal that proper attachment to the spindle has occurred, confirming it is safe to proceed to anaphase.
Prior to S phase (in G1), each human chromosome is composed of a single molecule of double-stranded DNA (one chromatid)
After S phase (in G2), each chromosome consists of two sister chromatids joined at the centromere
Kinetochores are not attached to the centromere until M phase
A diploid individual inheriting one copy of gene A from each parent has 2 copies per cell in G1
After S phase replication (in G2), that same cell has 4 copies of gene A
The key: count alleles per cell, not per chromosome
Cells are 4n (tetraploid DNA content) during part of S phase, all of G2, and part of M phase (before anaphase)
G1 cells are 2n
After mitosis, daughter cells return to 2n
G1 checkpoint: assesses readiness for DNA replication
S/G2 checkpoint: monitors DNA damage; a double-stranded break during synthesis halts the cell cycle here
Metaphase checkpoint (spindle assembly checkpoint): kinetochores signal that proper attachment to spindle fibres has occurred; this is the checkpoint found in late metaphase
Actively transcribed regions are found in the 10 nm fibre (beads-on-a-string) conformation, which is open and accessible
Heterochromatin, 30 nm fibre, and fully condensed chromosomes are transcriptionally silent or very low
If a double-stranded break occurs during synthesis, the cell cycle halts at the S/G2 checkpoint
The sister chromatid (not the homologous chromosome) is used as the template for repair during S/G2
Early anaphase involves cohesin cleavage, allowing sister chromatids to separate
Kinetochore attachment occurs earlier (during prometaphase/metaphase)
Condensin activation occurs during prophase, before anaphase
During meiosis I: 1 microtubule per pair of sister chromatids (monopolar attachment; both sisters go to the same pole)
During meiosis II: 2 microtubules per pair of sister chromatids (bipolar attachment, like mitosis)
During meiosis II, the tension holding sister chromatids at the metaphase plate comes from cohesin (not crossing over, not condensin)
During meiosis I, tension comes from a combination of chiasmata (crossover points) and cohesion between homologues
During metaphase, Aurora B kinase senses high tension from microtubules, confirming correct bipolar attachment
This is part of the spindle assembly checkpoint
Understanding cell cycle checkpoints is central to cancer biology. When checkpoints fail (e.g. p53 mutation), cells with damaged DNA continue dividing, accumulating mutations. Drugs targeting mitotic spindle assembly (like taxol) exploit the dependence on proper checkpoint signalling.
Students often confuse sister chromatids with homologous chromosomes. Sister chromatids are identical copies of the same chromosome, joined at the centromere. Homologous chromosomes are the maternal and paternal versions of the same chromosome.
Students frequently think microtubules attach to telomeres during M phase. They attach to kinetochores at the centromere.
Students sometimes believe that cells are 4n throughout all of interphase. G1 cells are 2n; 4n content builds during S phase and persists through G2 into early M phase.
Students mix up what provides tension during meiosis I vs. meiosis II. In meiosis I, chiasmata and cohesion between homologues provide tension. In meiosis II, it is cohesin between sister chromatids.
⚠️ Know the gene copy number at each phase: 2 copies of a diploid gene in G1, 4 in G2. This is a very common fill-in-the-blank.
⚠️ Be able to identify what phase a chromosome image represents based on whether it shows single chromatids, sister chromatids, or both homologues and sisters.
⚠️ The metaphase checkpoint (spindle assembly checkpoint) is specifically about kinetochore-spindle attachment, not about DNA damage.
⚠️ Cohesin cleavage = anaphase. If they ask what happens during early anaphase, the answer is cohesin cleavage.
⚠️ Microtubule attachment numbers: 1 per sister pair in meiosis I, 2 per sister pair in meiosis II.
True or False: Sister chromatids and homologous chromosomes are the same thing.
Fill in the blank: Cells have 4n DNA content during S phase (partial), ______, and early M phase.
True or False: Microtubules attach directly to centromeric DNA.
Fill in the blank: During meiosis I, there is/are ______ microtubule(s) attached per pair of sister chromatids.
True or False: Cohesin cleavage occurs during prophase.
Q: What is the point of attachment for kinetochore proteins that link chromosomes to microtubules?
A: The centromere.
Q: A person inherits identical copies of gene A on chromosome 10 from both parents. How many copies of gene A are present per cell in G1 and G2?
A: 2 in G1, 4 in G2.
Q: In which chromatin conformation would you most likely find actively transcribed DNA?
A: The 10 nm fibre (beads-on-a-string).
Q: What happens if a double-stranded break in DNA occurs during S phase?
A: The cell cycle halts at the S/G2 checkpoint.
Q: What provides the tension holding sister chromatids at the metaphase plate during meiosis II?
A: Cohesin.
Q: What would you expect to occur during early anaphase?
A: Cohesin cleavage, allowing sister chromatids to separate.
This material connects to chromatin and epigenetics (Part 3), since the condensation state of chromosomes determines transcriptional activity. It also feeds directly into DNA replication (Ch. 9), because replication occurs during S phase and the machinery must navigate chromatin structure. The checkpoint signalling involving p53 and cyclin-dependent kinases connects to the epigenetics and cancer content in the next section.
centromere, kinetochore, telomere, sister chromatids, homologous chromosomes, cell cycle, G1 phase, S phase, G2 phase, M phase, mitosis, meiosis, meiosis I, meiosis II, cohesin, condensin, anaphase, metaphase, spindle assembly checkpoint, Aurora B kinase, ploidy, 2n, 4n, DNA content, karyotype, microtubule attachment, bipolar attachment, monopolar attachment, chromatin conformation, 10 nm fibre, double-strand break repair