MODULE 1: cell cycle Flashcards

Question

degredation of mitotic cyclins (APC/C)

Answer 1

APC/C specificity changes in late anaphase once chromatids have separated Cdn1 becomes active and leads APC/C complex to mitotic cyclins for degredation this is necessary for chromatin decondensation and depolymerisation of microtubules --> needed to get to telophase

Answer 2

unplanned cell death

Answer 3

programmed cell death = common cell fate cell chopped up and packaged for removal. DNA is fractioned, cell membranes pinch off into small structures fragments are labelled for macrophages so that they will be cleaned up through phagocytosis apoptosis adjusts number of nerve cells to a target. survival factor released by target cells SIGNALLING PATHWAY CED-9 (protein) sits on mitochondrion and binds to CED-4 EGL-1 induces release of CED-4 from CED-9, initiating cell death CED-4 forms large octamer complex in cytoplasm interacts with CED-3 to form capsule holoenzyme capsule destroys vital proteins to cause cell death once active, CED-3: - cleaves lamins --> nuclear envelope dissolves - activates endonucleases --> DNA digested - attacks cytoskeletal structure - attacks cell-cell adhesion proteins - cleaves itself

Answer 4

tumours developed through selection process cancer cell has mutation with growth advantage selection of cell with growth advantage= more mutations

Answer 5

normally promote cell growth once mutated (typically gain of function) or amplified they become oncogenes (Ras, myc, src) can duplicate DNA

Answer 6

early pollops can be identified and removed stages I-III = benign right before stage IV, p53 activated = cell death, cell cycle arrest, sensescence common genes mutated along progression APC (adenoma polyposis coli protein) ------| wnt signalling -----> myc proto-oncogene -----> proliferation advantage (benign) Ras (growth factor) -----> MAPK (mitogen activated protein kinase) -----> proliferation

Answer 7

spread of cancer cells from their site of origin and establishment of secondary growth most cancer deaths arise from metastasised tumours as more cells become mutated, they can detect GFs and move towards source 1. penetrate basement membrane by acquiring enzymes 2. migrate on ECM fibre down to blood vessel 3. travel to anywhere in body (1 in 1000 land somewhere to make tumour)

Answer 8

rare childhood cancer if caught early, 95-98% cure rate caused by mutations in Rb gene 1) hereditary retinoblastoma - RB+ and RB- (from parents) - somatic mutation - RB- and RB- - homozygous cells give rise to tumours in retina 2) sporadic retinoblastoma - RB+ and RB+ - two somatic mutations - RB- and RB- - homozygous cells give rise to tumours in retina

Answer 9

cell is committed to another round of cell division once it passes restriction point and is no longer mitogen-sensitive 8 hours between restriction point and S phase - cell can still exit cycle within this period Rb is a transcriptional repressor of E2F (a TF of genes required for DNA replication). Rb is also a substrate for G1 cyclin/CDK. hyper-phosphorylation of RB = restriction point passed, cell mitogen-independent and committed to cell cycle

Answer 10

APC/Cdh1 degrades mitotic cyclin so DNA can be decondensed = region of gene called destruction box APC/Cdh1 can degrade many proteins required for S-phase (such as E2F) so it needs to be inactivated before cells enter S-phase - APC inactive at G1/S boundary - APC inactive in S phase - APC active in mitosis - region between inactive APC and start of DNA replication = cells cannot exit cell cycle = new committment point G1/S CDK phosphorylates Cdh1 Emi1 leads another Ub ligase to destroy Cdh1

Answer 11

cell stress -----> p16 -----| G1 cyclin/CDK (cyclin D + CDK4) -----> Rb -----| E2F -----> transcription of genes that control entry into S-phase - under stress, p16 sits atop G1 cyclin/CDK complex - this prevents CDK/cyclin complex from hyper-phosphorylating Rb - Rb sits atop E2F to prevent gene transcription - no hyperphosphorylation = no Rb release from E2F = no gene transcription in presence of mitogens, p16 is inactive --> G1 cyclin/CDK active --> Rb phosphorylated and removed from E2F --> E2F transcribes genes for S-phase ``` cancer cells frequently: - delete/inactivate p16 - over express/amplify G1 cyclin - delete/inactivate Rb tumours have only one of these mutations, indicating that regulation of this genetic pathway needs to be disabled for growth ```

Answer 12

p53 = tumour supressor detects conflicts within cell (DNA damage, telomere shortening, etc) and can activate several different pathways to resolve conflicts (cell cycle arrest, apoptosis) ATR ---| MDM2 ---| p53 - p53 controls WAF1 gene - an inhibitor of CDKs - therefore, p53 activity inhibits cell cycle progression - MDM2 degrades p53 cancer cells have GOF mutation in MDM2 or LOF mutation in p53 = excessive proliferation 50% of tumours have mutations in p53 pathway/gene

Answer 13

transcriptional regulation: distinct genes turned on/off controlled via various mechanisms translational regulation: distinct mRNAs translated or repressed and localised to different regions of cell epigenetic regulation: marks on DNA that regulate gene expression are inherited by daughter cells but independent of DNA sequence

Answer 14

cells contain factors which provide unique info related to cell factors localised to particular region of cell cell divides to produce two identical cells in terms of DNA, but different regarding cytoplasmic contents

Answer 15

cell fate determined bu interactions with neighbouring cells - back cells in blastula form back tissue - transplant these back cells into belly regions - these cells then go on to form belly tissue

Answer 16

morphogen gradients are typically TF's that are "master gene regulators" i.e. determine whether it is head or tail region of animal example: drosophila embryos - bicoid = head and nanos = tail - mother deposits mRNA in unfertilised egg - egg already polarised - mRNA localised at poles of egg - egg fertilised, DNA replicated with no cell membranes ---> gradients of cell specificity factors - exposure to amount of factors determines cell fate bicoid and nanos are tranlational inhibitors and transcription factors inhibity translation of two other mRNAs involved in early patterning of embryo, hunchback and caudal hunchback and caudal not localised bicoid binds to caudal and prevents it being made into protein (same re. nanos and hunchback)

Answer 17

Dna contains elements that allow for cell specific gene regulation TFs - proteins that promote or inhibit gene expression enhancers - TF binding sites histones - proteins that package DNA and can be modified to regulate gene expression. positively charged tails interact with negative phosphate backbone of DNA epigenetic marks - histone acetylation and methylations as well as DNA methylation. modify histones to allow DNA translation acetyl and methyltransferases - enzymes that add epigenetic marks to histones and DNA in general, modifications that decrease histone tail interactions with DNA open up the chromatin acetylated histones --> open chromatin, transcriptionally active deacetylated histones --> close chromatin, transcriptionally silent

Answer 18

permanent cell cycle exit differentiated cells become refractory to proliferative signals (respond in different way) G1/S CDK inhibitor and Rb family members play major role in cell cycle exit terminal differentiation distinct from senescence cell fate determining TFs * - ----> G1/S CDK inhibitors - ----| substrates for cycling CDKs become dephosphorylated (less phosphorylated Rb) - ----> Rb recruits epigenetic modifying complexes that permanently repress E2F transcriptional activity * cell fate inhibits cdc25 and activates eigenetic regulators. Rb recruits epigenetic regulators to locus in genome and mark histones and DNA to permanently silence it

MODULE 1: cell cycle Flashcards

(42 cards)