BIOL1025 - Spindle Assembly Checkpoint and mitosis Flashcards
SAC
spindle assembly checkpoints
APC/C
inactive until kinetochores are properly attached to the MT
SAC function
keeps APC/C inactive during prometaphase
After proper attachment of MT to kinetochores are made
APC/C activated and performs 2 major functions
2 major function of when APC/C is activated
Ubiquitinates Securin
ubiquitinates cyclin B
Ubiquitinates Securin
after securin destruction - releases/activates separase
which removes cohesin (cleavage) from centromere - triggers anaphase
Ubiquitinates cyclin B
after cyclin B destruction - inactivatesCdk1 therefore leads to mitotic exit
cohesion of sister chromatids
established after DNA synthesis
cohesin and DNA catenation responsible for this
during S phase
mitosis stages
prophase, prometaphase, metaphase, anaphase, telophase and cytokinesis
prophase
replicated chromosomes - sister chromatids condense
mitotic spindle assembles between 2 centrosomes that have been replicated and moved apart
prometaphase
breakdown of nuclear envelope (NEBD)
chromosome attach to spindle MT via kinetochores and undergo active movement
prometaphase of cell
nuclei dissolves - open mitosis
closed mitosis
nuclei in cells remain intact - not complete breakdown of nucleus
metaphase - chromosomes
aligned at equator of spindle - midway between spindle poles
metaphase - kinetochores MT
attaches to sister chromatids to opposite poles of spindle
anaphase - sister chromatids
synchronously separate to 2 daughter chromosomes and pulled slowly to spindle poles it faces
anaphase - kinetochores MT
gets shorter and spindle poles move apart
both processes contribute to chromosome segregation
telophase - chromosomes
2 daughter chromosomes arrive at poles of spindles and decondense
telophase - nuclear envelope
new nuclear envelope reassembles around each set = complete formation of 2 nuclei and end of mitosis
telophase - spindles and cytoplasm
central spindles are formed
division of cytoplasm begins with contraction contractile rings
cytokinesis
cytoplasm divide by contractile ring of actin and myosin filaments
by pinching cells in 2 daughter each with one nucleus
mitotic spindle assembly
MT have inherent polarity
mitotic spindle assembly - dynamic nature of MT
slowly depolymerisation at negative end and rapid polymerisation/depolymerisation at positive end
drug inhibitor
such as colchicine
function of colchicine
binds to alpha-beta-tubulin interface and blocks polymerisation of MT- shortening and depolymerisation of MT at metaphase
kinetochores
large multiprotein complexes responsible for attachment to MT of mitotic spindle - assembled on centromeric chromatin
lack of proper connection between kinetochore and MT fibre cause
activation of SAC and induces cascade of events - inhibiting APC/C
function of inhibited APC/C
stop progression of mitosis in metaphase - gives cells more time to repair/generate proper attachments between MT and kinetochores
inhibiting APC/C allows…
protection against improper segregation(mis-segregation) of chromosomes
cells treated with MT destabilisers such as colchicine
cells accumulate all phase up to and including metaphase and won’t progress until drug is removed
how kinetochores are assembled
early during mitosis on centromeres
how centromeres are assembled
part of chromosomes where primary construction - fragment of DNA which allows chromatid segregation during mitosis
where kinetochores are assembled
region on chromosomes
human kinetochores function
multiplies MT to form connection between mitotic spindle and chromosomes
inner kinetochores
sits close to centromeric chromatid
outer kinetochores
binding to MT to mitotic spindle
positive end of MT
project away from spindle pole
negative end of MT
anchored at spindle poles
kinetochores MT
connect spindle poles with kinetochores of sister chromatid
interpolar MT
form 2 poles interdigitate at spindle equator
astral MT
radiates out from poles into cytoplasm and frequently contact cell cortex
segregated chromosomes
packaged in daughter nuclei at telophase and entire cell divides - cytokinesis
mitotic cyclin
destroyed and other proteins that well phosphorylated at entry to mitosis is dephosphorylated
end of mitosis
chromosomes decondense and cells centre interphase
