cell cycle Flashcards
division in specific cells
cells divide at different rates eg embryonic vs adult cells depends for necessity for renewal eg intestinal cells
cell division in tumours
apart from mutations in TMS/aneuploidy, solid tumours are aneuploidy (abnormal chromosome number)- contact inhibition of growth (when cells know when to stop growing) not present, of protein levels of cell cycle regulators affected
stages of cell cycle
interphase (duplication)- not just DNA, but also organelles and protein synthesis M phase ie mitosis: nuclear and cytoplasmic (cytokinesis) division coordination
vulnerable period of cell cycle and why
M phase, as cells more easily killed, and DNA damage can’t be repaired
phases of interphase
G0- cell cycle machinery broken down, cell resting G1 (gap)- decision point S- DNA/protein synthesis+ replication of organelles G2 (gap)- is all DNA produced
centrosome
double barrel composed of 2 centrioles- forms microtubule organising centre and (polymerisation of them occurs from them) mitotic spindle
DIAGRAM what occurs in prophase
chromatin condense- forms two sister chromatids with a centromere in the middle, with kinetochores on each side centrosomes also go on opposite side
DIAGRAM spindle formation and interaction
radial microtube arrays (called asters) from AROUND each chromosome, and meet in the middle to form polar microtubles
early prometaphase
early- nuclear breaks down, which spindle formation having already occurred: chromosomes attach to spindle microtubules via KINETOCHORES
late prometaphase
chromosomes attached to each pole go to middle
DIAGRAM anaphase and subphases
sister chromatids separate (COHESIN hold chromatids together) anaphase A- cohesion broken down, microtubules contract and get shorter anaphase B- DAUGHTER CHROMOSOMES pulled to opposite poles AND spindle poles (centrosomes) move outwards
telophase
daughter chromosomes arrive at spindle, nuclear envelope forms again, and contractile ring forms (needed for cytokinesis)
spindle assembly checkpoint and proteins needed- also where occurs
make sure that chromosomes are aligned at equator, and that chromosomes are attached to microtubules- occurs between prometaphase and metaphase needs BUB kinases and CENP-E
DIAGRAM misattachment of microtubules to kinetochores- types and overall
monotelic attachment- only 1 sister chromatid attaches syntelic- both chromatids attach to same tubule= go to same daughter cells/pole merotelic- multiple microtubules attach to same sister chromatid= chr LOSS in cytokinesis leads to aneuploidy amphelic- normal
aberrant centrosome/DNA duplication
leads to more than 2 centrosomes= more than 2 daughter cells= aneuploidy
how anti-cancer therapy works and examples and their mechanisms
cause GROSS chromosome missegregation, meaning cells is unviable so dies chekpoint kinase (checkpoint in G2) inhibitors taxons and vinca alkaloids change microtubule mechanicsms, unattached kinetochores, and long term mitosis (ie more vulnerable)
what happens in sth goes wrong during cell cycle
cell cycle arrest at checkpoints: often temporary OR apoptosis if DNA damage too great/chromosome abnormalities
DIAGRAM how tumours affects checkpoint
growth factors affect G1 checkpoint, allowing S phase to occur- tumour affect this tumours also effect G2 checkpoint (for DNA damage) or metaphase checkpoint (for alignment)
G0 and how tumours affect it
tumours also prevents exit of cell cycle at G0, so no resting state in this stage, cells are not dividing, but are NOT dormant the exit from G0 back into cell cycle needs growth factors, which activates a signalling cascade
DIAGRAM how peptide growth factors work
dimeric ligand binds to a monomeric receptor, forming dimers, as the 2 kinase domains brought together and are phospohrylated receptor protein tyrosine kinase involved, activating the receptor
how phosphorylation occurs
negative phosphate from ATP added to hydroxyl group of serine, threonine or tyrosine- causes change in shape- doesn’t just phosphorylate kinase domain, but also other sites too, causing a kinase cascade
kinase cascade
kinases are regulated by other kinases- 1 kinase is phosphorylated, and it phosphorylates a second kinase this phosphorylation is reverse by PHOSPHATASES
