Cell Division Flashcards
Andrew Holland Lecture 2
5 Stages of Mitosis
IPMAT
Interphase, Prophase, (Prometaphase), Metaphase, Anaphase, Telophase
Define: Centromere
chromatin that defined the site of microtubule attachment in mitosis. Confers mitotic stability
Define: Kinetochore
multi proten complex that assembles on centromere, binds microtubules
4 types of centromeric location
telocentric, acrocentric, submetacentric, metacentric
What is the centromere paradox?
Centromere confers mitotic stability, but the sequence is not conserved across species. Specific nucleosomes actually define the centromere.
CENP-A Function
H3 histone variant that is found at centromeres. Defines centromeres in higher eukaryotes
Cryptic Centromeres
Centromeres found in chromosomes from chromosome fusion events in evolution
Neocentromeres
Shows centromere sequence is not necessary for identity. Epigenetic acquisition of new centromere site when original site is deleted.
CENP-B/C
Marks location of original centromere when neocentromeres are used
α-Tubulin, β-tubulin Function
Tubulin monomers that form heterodimer
GTP-Tubulin Function
Bind at end of GDP-Tubulin to cap microtubule
MT Catastrophe Mechanism
GTP-tubulin cap is hydrolyzed to GDP-Tubulin
Protofilaments peel apart
MT Rescue Mechanism
GTP-tubulin caps MT to prevent protofilament peeling
GTP-tubulin keeps getting added as soon as GTP-tubulin on cap gets dephosphorylated
What is the PCM?
Pericentriolar matrix
γ-Tubulin Function
Located in PCM, provides template for nucleation of MTs. lowers energy barrier for MT formation
Centrosome Function
Microtubule organizing center in animal cells
Centrosome Components
Centrioles, Microtubules, PCM.
How do supernumary centrosomes form?
When centrioles divide more than once, more than one centrosome can be created.
What allows chromosome movement during the cell cycle?
Depolymerization of microtubules attached to kinetochores
Function: Cohesin
Tripartite ring that holds sister chromatids together by topologically embracing molecules
Structure: Cohesin
Smc1, Smc3, Scc1 (cleavage site)
T/F. Sister chromatid disjunction is a seperable event from mitotic exit.
True
Function: APC/C
Coordinates anaphase with mitotic exit by ubiquitinating Cyclin B1 and Securin
Function: Cyclin B1
Needs to be degraded for mitotic exit
Function: Securin
Binds to Separase and will not release until it is degraded upon ubiquitination by APC/C
Function: Separase
cleaves Cohesin at Scc1 site (Kleisen) to allow sister chromatid disjunction
Mechanism: Sister Chromatid Disjunction
1) APC/C^Cdc20 gets activated, ubiquitinates Securin and Cyclin B1
2) Degraded Securin allows Separase to cleave Cohesin at Kleisin (Scc1)
3) Sister chromatid can separate
4) Cells exit mitosis after degradation of Cyclin B1
Function: MAD1
Release inhibitory signal that will activate MCC when MTs are not attached to kinetochore
Function: MCC
Inhibit APC/C
Mitotic/Spindle Assembly Checkpoint
1) Unattached kinetochore still has MAD1
2) MAD1 release signal, activates MCC, which inhibits APC/C
3) One all microtubules attach, MAD1 is released from kinetochore
4) MCC is no longer functional once MAD1 is released from ALL kinetochore
5) APC/C can ubiquitinate Securin and Cyclin B1
4 Types of Erroneous MT Interactions
Amphitelic (normal), Monotelic (release diffuse inhibitory signal), syntelic, merotelic
Function: Aurora B
kinase at centromere that senses tension.
Low tension applies, phosphorylates components of outer kinetochore
Tension: Does not phosphorylate
What type of division occurs in Meiosis I?
Reductional Division
What type of division occurs in Meiosis II?
Equational Division
How is cohesion lost in two distinct steps in Meiosis?
In meiosis 1, separase cleaves cohesins found in arms, but Sgo1 is still present at centromeres
In meiosis 2, separase cleaves cohesins (Sgo1) present at centromeres.
What chromosomal state to tumors have?
Aneuploid, due to supernumary centrosomes that facilitate merotelic attachment
