Cancer 2: cell cycle Flashcards
Do all cells divide at the same rate?
NO
embryonic cells-very fast (30min per divide in frog embryo)
Complex systems take longer
Necessity for renewal-intestinal cells -20h, hepatocytes-1y -but can regenerate livers in necessities
Stage of differentiation-some never divide-neurons/cardiac myocytes-or some often (hair, etc)-why chemo attacts them first
TUMOUR cells-follow no rules-lose the ability to control all of it
What happens to normal cells with abherrent mitosis? What about cancer cells? what does it mean for treatment?
Usually results in cell death-
So need mutations in oncogenes and Tumour supressor genes
Most tumours are aneuploid (abnomral Chr number/content) and have Chr instability (lose and gain Chr in division)
Also mitosis protein regulators vary in tumour-abnomral mitosis
Normal cells have contact inhbition-space limitation-and in cancer this is often lost
—> cancer treatment best-target chromosome segregation
What are the 3 phases of the cell cycle? When are cells the most vulnerable?
Duplication, division (and general co-ordination of them)
Pretty much - M-phase-divison and interphase (duplication of Chr, but also organelles, proteins,)
M phase very short compared to interphase-
(remember - G1-S-G2-M-etc – with possible escape to G0-where the cell is active normally)
Most vulnerable during mitosis-cell are more easily killed-any damage cant be repaired, no protein transcription, low metabolism
Recall the 4 parts of the cell cycle?
(remember - G1-S-G2-M-etc – with possible escape to G0-where the cell is active normally
G0-active G1-like a check book checking if all is ready S-dupliacte DNA G2-second check of everything M-mitosis- G0-active
What happens during the S phase?
DNA replication-
Increase protein synthesis-initiation of translation and elongation increased-capacity increased
Relication or organalles-centsosomes, mito, golgo, etc)–and also duplicate mito DNA
What is the centrosome? What is it used for?
Two centrioles at 90o from one another–
Mainly microtubule structures with proteins around to hold them together
Act as Microtubule organising center (MTOC)
Duplicated in S phase-each barrel splits and gets an extra barrel each
Act as co-ordinators of mitosis-pulling the DNA each side etc
What happens during prophase?
Condensation of the chromatin-get from DNA to CHr
arrange along histones, then beads on a string, then pack in chromatin (30nm wide)-extended scaffold-300nm)-then condensed again to form the Chr
Each CHromosome centromere (made from a kinetochore that acts like a belt on the Chr) a the center of sister chromatids
In late prophase-centrosomes at each apex of the cell-opposite each other-with the Chr around the center
Spindles form outiside of nucleus and link the centrosomes together
How do centrosomes form spindle? why how?
Start as radial microtubules (all around them)-then the array meet-connect and then centrosoe start polarising microtubules towards the point where they met
What happens during metaphase?
Chromomes are aligned at the equator of the spindle-
Prometaphase can be cut into two: early and late
Early-breakdown on nuclear membrane (release the Chr)-spindle is largely complete-Chr attatched to spindle via kinetochore
late-microtubule from opposing pole is captured by sister kinetochore
chr attatched to each pole go to middle-Chr slide rapidly toward center along microtubule
What happens during the Anaphase?
paired chromatids speratate from another-pulled to each side to form the daughter chromosomes
The cohesins that holds the chromatids is broken down
can be broken down in A and B
anaphase A-cohesion broken down, microtubules get shorter-each daughter chr is pulled towards the centrosomes/spindle poles
Anaphase B-Daughter migrate toward the spindle Poles AND the spindle poles are being pulled out/away from each other as well
(some microtubules still connect to the other side_
What happens during telophase?
Daughters chr arrive at the spindle
Nuclear envelop starts to assemble at each pole
assembly of contractile ring (to pinch the cytoplasm out)-made of actin and myosin-around the cleavage furrow
What happpens during cytokinesis?
Contractile ring formed and tightens-some microtubules still corssing across until cut
Chromosomes are still present and nucleus still forminh
What is the first checkpoint cells have to pass to divide?
Metaphase checkpoint-between prometaphase and metaphase–check completion of alignement and spindle assembly
Senses by kinases attatched to the kinetochores-if not attatched properly-send a signal -only when all are attatched can the division continue
Needs CENP-E and BUB protein kinase (leaves when attatched well_
Why is it important to have a metaphase checkpoint?
because if all Chr arent attatched, then some would be only pulled by one side-abnormal amount of Chr in the cells (one will get both sister chr, one will get none)
4 types-monotelic attatchment (attatch only to one side)
Merotelic-one centro attatches to both side of the chromosome AND the other one also has one side (compete for same chromatid-lose it during cytokinesis)
Amphelic-normal
Synthetic attatchment-both sides of Chr atttached to cables coming to SAME centromere
=> leads to aneuploidy
What other routes to aneuploidy is there?
Wierd centromere attatchments
Also Aberrant centrosome/DNA duplication-
centrosomes (too many/too little), dont go to the right place-et
all very bad for cell-why is a cancer therapy
