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5/11/2017 Recap on Regulation of Mitotic Events Cell Cycle Regulation (part2) a |i i oa tn 5 est a te Bio 150 lecture ‘ a Sonia D Jacinto Protas Sepa? 1 Chromerome ere Einar connor Institute of Biology 2 Formonst — — Sunt of dj rcarreetoe UPiliman ‘wieder Miss ary APE 2 aoen of keene DNA synthesis in mammals needs cyclin A + cak2-cyclina ~ triggers prereplication complex as ins. bits formation of another prereplication complex “Homologue of Cde28/cyclin 85/6 Con Cell Cycle Control in Mammalian yas one Cells retain sarann \* + cel eyting follows i comah ~ Exrocllrcues onthe narber an ent of (Cy ig EBD, seighborng ce) a > tcl ceo ie 8 deepen ae Most withdraw frm G1 to gto eifferetiate and become postmitoicells; some never enter Mt phase 930 5/11/2017 ‘Gene Expression in Mammalian Cells upon Entering Cell Cycle from Gy + Foriyresponse- transcription factors that ‘cause transcription of late response genes 8 CFosand Cun + Lote response ~ E62 cyclinD and, ck 2, 4,6 "ane acaton of Rear ary respon gee (CF and Cu) Rb-E2F role + Atresting conditions, Rb sequester E2F {tansripton factor within te eos + Phosphorylation of Rb > dissociation ofthe Rb- 2Fcomplex > E2F translocate othe mies + Inthe nucleus, £2 bind othe promoter resin ‘ofa numberof genes that prime the el to ‘rogressinto the phase of the cycle e-m, ‘lin AVE and COKITede2), amongst oer Cyclin dependent kinase inhibitors (CIP) in ‘Mammalian Cells nomologues tc inyut) ~Cék inhibitory proteins (CIP); ¢.g. 621, 27, p53, p57 “Released in cesponte to ONA dma —INK4 “inhibits only edka/eyclin D and cdk6/eyclin ; p16 an INK 4 is a tumor suppressor S/11/2017 Cell cycle checkpoints —_—— aS = > | miner cmebtsttetremamimnneuncmarsntimiein | ‘Checkpoints: Quality Control of the Cell Cycle (cont'd) spindle checkpoints: detect any failure of spindle fibers to attach to kinetochoresand arrest the cell in metaphase (M checkpoint) ~ detectimproper alignment of the spindle seit andbock cytokinesis, = wiggerapoptsis if damages ireparabl, CHARACTERISTICS OF NORMAL CELLS Limited proliferation capacity: somatic Cells are subject to the Hayfick limit (Hayflick, Exp. Cell Res. 37 614 (1965) Up to 40-50 divisions before undergoing senescence and death, Due to telomere ‘erosion and end replication problem Anchorage dependence: proliferation requires binding via integrins to (ECM) ‘components, CHARACTERISTICS OF NORMAL, CELLS (cont'd) Contact inhibition: contact with lke cll types Inhibits cel movement and protferation, form quiescent G, cel, monolayers in eal cute. Contact with unlike cel allows ‘motity and hence spontaneous cell srting, Growth factor dependence: proliferation depends on| ‘availabilty of growth factors; factor withdrawal leads to apoptosis. Growth in serum-rich or Condtioned media (autocrine factors, plating ensty dependence of growth), Cell Cycle and Apoptosis * Apoptosisiso form of programmed cell death which may result from irreparable NA damage 5/11/2017 Characteristics of apoptosis + Membrane blebbing + Nuclear condensation->DNA fragmentation + cell shrinkage + Detachment from substrate + Breaking up into apoptotic bodies Uncontrolled Cell Cycle and Diseases + Excessive poptosismay cause diseases such as Parkinson's & other neurodegenerative disorders + When apoptosis falls and celles to M with unrepaired DNA damage transformation/cancermay result TRANSFORMATION |Immortalization and aneuploidy: survival and Continuous growth beyond normal ims involves ‘changes atthe telomere that frequently resuit in ‘major chromosemal rearrangements Partial or complete loss of growth factor ‘dependence: growth on less rh serum, ‘or at lower inal cell density Loss of contact inhibition: overgrowth of ‘monolayers, Loss of anchorage requirement: growth on soft ‘gar orn suspension Semen renee i +30 | 5/11/2017 Radiation Chemical Carcinogen Tumor suppressors 52a senor of DNA damage | ee pee swe et tp hao tap Sree eT ent me? watt rope sipreiemeranrs

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