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 9305/11/2017
‘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
suppressorS/11/2017
Cell cycle checkpoints
—_——
aS =
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‘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 damage5/11/2017
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
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+30
|5/11/2017
Radiation Chemical Carcinogen
Tumor suppressors 52a senor of DNA damage
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