Centrosomes, Kinetochores. Chromosome segregation II Flashcards
What is the microtubule-organising centre
- called a centrosome in animal cells
- spindle pole body in yeast
- two centrioles organise the centrosome matrix, forming a centrosome
- gamma-tubulin complex gives nucleation sites of MTs
- MTs extend from MTOCs with the distal plus end
Structure of the y-tubulin complex
- 7 copies of y-tubulin small complexes are arranged in a spiral
- provides template for MT nucleation
Structure of centriole
- 9-fold symmetry
- triplets of short MTs are arranged around the cartwheel structure
S/G2 centrosome duplication
- stimulated by S-CDK
- mother centriole promotes elongation of a daughter centriole
Early prophase centrosome duplication
- aster formation
- centrosome separation
Late prophase-prometaphase centrosome duplicaiton
mitotic spindle is formed between two centrosomes
How do microtubules attach to chromosomes
- MT plus end attaches at the Kinetochore
- Kinetochore has a plate-like structure
- each chromatid has only one kinetochore
Kinetochore attachment in metaphase
single kinetochore attaches to a single MT in budding yeast, whereas single kinetochore attaches to 20-30 MTs in humans
Structure of centromeres in EU cells
- chromosome regions supporting kinetochore assembly
- structure varies among organisms but CENP-A nucleosomes are commonly found
- point centromeres in budding yeast are defined by consensus DNA sequence
- regional centromeres in others are maintained by CENP-A-dependent epigenetic mechanisms
Where are centromeres in vertebrate cells
embedded in heterochromatin
Structure of kinetochore in budding yeast
Structure of kinetochore in humans
Process of kinetochore-MT interaction
- Kinetochore capture by lateral surface of MT (lateral attachment) (pro-meta)
- MT-dependent kinetochore transport towards a spindle pole (end-on attachment) (pro-meta)
- Both sister kinetochores interact with MTs from the same or opposite spindle poles (pro-meta)
- Sister kinetochore bi-oientation (metaphase)
How is lateral attachment converted to end-on attachment
Key molecules in budding yeast
- Ndc80 complex: direct MT attachment
- Dam1 complex: tethers kinetochore at the MT end
Errors in chromosome bi-orientation during chromosome segregation
- can lead to merotelic attachment
- threat for dividing cells as it occurs in early mitosis
- can lead to chromosome mis-segregation and aneuploidy
Define monotelic attachment
(mono-orientation) when one single pole and kintochore-microtubule is attached to the chromosome, occurs before metaphase
Define amphitelic attachment
(bi-orientation) when two spindle poles and kintochore-microtubule are attached to the chromosome during metaphase
Define syntelic attachment
(mono-orientation) when a spindle pole binds two sister kinetochore-microtubules of the singular chromosome
Define merotelic attachment
error occurring when a single kinetochore is attached to microtubules emanating from both spindle poles
Define merotelic attachment
error occurring when a single kinetochore is attached to microtubules emanating from both spindle poles
Role of Aurora-B kinase in error correction
- phosphorylates Dam1 which weakens association with Ndc80C
- disrupts end-on attachment
- promotes exchange to new MT lateral attachment
- establishes bi-orientation
- kinetochores delocalise from aurora B
- kinetochore components are dephosphorylated
- kinetochore-microtubule is established
- tension is generated by cohesin
