(/cellbiology/index.php/File:Cell_cycle1.jpg)The Cell Cycle in relation to cyclin levels

Cell Cycle

Cell CycleIntroductionThis lecture will introduce thecell cycle, which is the entirelife of a cell from birth todeath. This overall topic is toolarge for a single lecture, sowill focus on ourunderstanding of theregulation of the cell cycle.Later lectures will coverconcepts on cell birth (celldivision), differentiation(signaling, development) anddeath (2 lectures) in moredetail.

Lecture Slides: 2017 LecturePDF(/cellbiology/images/b/bf/2017_Cell_Cycle.pdf)

ArchiveMH - note that content listed below will not match exactly current lecture structure but has beenselected as having similar content.

2016 (https://cellbiology.med.unsw.edu.au/cellbiology/index.php?title=Cell_Cycle&oldid=66800) |2013 (http://php.med.unsw.edu.au/cellbiology/index.php?title=Cell_Cycle&oldid=44633) | 2009Lecture 15 (/cellbiology/index.php/2009_Lecture_15)

Textbook - Molecular Cell Biology

Section 13.1O verview of the Cell Cycle and Its Control(https://www.ncbi.nlm.nih.gov/books/NBK21466/)Fig 13.2 Current model for regulation of the eukaryotic cell cycle(https://www.ncbi.nlm.nih.gov/books/NBK21466/figure/A3467/?report=objectonly) | Cell cycleregulation animation (/cellbiology/images/6/66/Cell_cycle_regulation.mp4)

Objectives

Understanding of the main stages of the cell cycleBroad understanding of different cell lifespanUnderstanding of the differences between embryonic and adult cell cyclesUnderstanding of the key regulators of cell cycle

cyclinscyclin dependent kinases

Broad understanding of abnormal cell cyclesHow the cell cycle is monitored

Background ReadingNature - Cell Division Milestones (http://www.nature.com/celldivision/milestones/index.html)

Recent Nobel Prizes2001 - Control of the Cell Cycle(http://nobelprize.org/nobel_prizes/medicine/laureates/2001/index.html)

Leland Hartwell (born 1939), Fred Hutchinson Cancer Research Center, Seattle, USA, isawarded for his discoveries of a specific class of genes that control the cell cycle. One ofthese genes called "start" was found to have a central role in controlling the first step of eachcell cycle. Hartwell also introduced the concept "checkpoint", a valuable aid to understandingthe cell cycle.Paul Nurse (born 1949), Imperial Cancer Research Fund, London, identified, cloned andcharacterized with genetic and molecular methods, one of the key regulators of the cell cycle,CDK (cyclin dependent kinase). He showed that the function of CDK was highly conservedduring evolution. CDK drives the cell through the cell cycle by chemical modification(phosphorylation) of other proteins.Timothy Hunt (born 1943), Imperial Cancer Research Fund, London, is awarded for hisdiscovery of cyclins, proteins that regulate the CDK function. He showed that cyclins aredegraded periodically at each cell division, a mechanism proved to be of general importancefor cell cycle control.

1989 - Cellular Origin of Retroviral Oncogenes(http://nobelprize.org/nobel_prizes/medicine/laureates/1989/index.html)

Michael Bishop and Harold Varmus used an oncogenic retrovirus to identify the growth-controlling oncogenes in normal cells. In 1976 they published the remarkable conclusion thatthe oncogene in the virus did not represent a true viral gene but instead was a normal cellulargene, which the virus had acquired during replication in the host cell and thereafter carriedalong.

Prokaryote DivisionBinary Fission - and seen in eukaryote mitochondriaAsexual reproduction - replicates original cell to produce two identical cellsGrow in numbers exponentially - adequate nutrients and a fast life cycle

(/cellbiology/index.php/File:Escherichia_coli.jpg)Escherichia coli

single organism can multiply into billionsHigh mutation rate of bacteria

Appear to involve proteins that are homologsof eukaryotic cytoskeleton proteins.Prokaryotic Cytoskeleton Filaments

(/cellbiology/index.php/2009_Lecture_9#Prokaryotic_Cytoskeleton_Filaments)

Cell LifespanBody Cell Types - about 210 typesLifespan

BornDifferentiateFunctionDie or Divide

Cell Lifespan ExamplesIntestinal epithelial cells 3–5 daysRed blood cell 120 daysBrain neuron, heart 50 - 100 yearsNeutrophil

in circulation 6-7 hoursin tissue 4 days

Epidermis Example

(/cellbiology/index.php/File:Epidermis_cartoon.jpg)(/cellbiology/index.php/File:Skthin040he.jpg)

Lifespan ProcessesBirth - Mitosis (except germ cells - Meiosis)Growth - Expression of genes and proteins required to grow the cell, its organelles andcytoskeletonFunction - Expression of tissue specific genes and proteinsDivision - DNA during cycle, whole cell in MitosisDeath - Apoptosis (programmed cell death) Necrosis (un-programmed cell death)

Movie - Embryo Mitosis(https://embryology.med.unsw.edu.au/embryology/images/a/a3/Blastomere_mitosis_01.mp4) |Movie - Cell Death (Apoptosis)(https://cellbiology.med.unsw.edu.au/cellbiology/images/a/a5/Apoptosis_movie_1.mp4)

(/cellbiology/index.php/File:Apoptosis_cell_culture.jpg)

Cell Cycle Major PhasesMitosis (M phase)

Cell birth(division) small time of cell cycle

InterphaseMost cell life Cell growth, function DNA synthesis organelle development

Cell Cycle

Time cell comes into existence until that cell divides againRapidly growing human cells 20-24 hrLiver cells 1-2 yearNeurons 1 onlyQuiescent G0

Cell Cycle- Stages

Rapidly dividing cell (20-24hr)

MitosisM phase 1 hr

InterphaseG1 Phase

cellular growth 9hrMost variable timeCan exit to G0

S PhaseDNA duplication 9hr

G2 Phasegrowth prepare formitosis 4 hr

(/cellbiology/index.php/File:Cell_cycle1.jpg)Cell Cycle Phases

Cell Cycle DifferencesEarly Embryonic Cycle

no growth occurseach daughter cell is half the size of parent cellcycle time is very shortS phases and M phases alternate without any intervening G1 or G2 phases

G0 Phaseexits the cycle at G1 (cancer cells do not enter G0)cell can leave the cell cycle (temporarily or permanently)temporarily - quiescentpermanently - terminally differentiated

cell will never reenter the cell cyclecarry out their function until they die

not simply the absence of signals for mitosisactive repression of the genes needed for mitosis

Stem Cellspluripotent self-renewal cell cycle of human embryonic stem cells (hESCs)short G1 period without reducing periods of time allocated to S phase, G2, and mitosis.Differences between pluripotent and lineage committed cell cycle length(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667593/figure/F1)

Central Nervous Systemdevelopment requires extensive progenitor cell proliferation (Neural stem cells, NSCs) PMID24859217closely followed by differentiation (neurons and glial cells)

gives rise to differential growth and cellular diversity

Cell Cycle RegulationCell proliferation is strictly regulated

Unregulated/abnormal proliferation is oncogenesis or Cancer

An overview of the cell-cycle control system (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.3243)

Cell Cycle- External RegulatorsCell replacement in different tissues

regulated by growth factorscan be specific for specific cell types

Growth Factors and Cell Cycle ProgressExternal factors can also regulate progression through cycleGrowth factors primarily act on cells in G0 and G1The restriction point is the timepoint in G1 when cells no longer respond to withdrawal ofgrowth factors by returning to G0, but progress to S phase.

thought to involve retinoblastoma protein (pRb)Restriction Point(http://journals.prous.com/journals/dof/20032809/html/df280881/images/Kong_f1.gif)

Growth Factor ModelFibroblasts in culture

Serum (Prepared by clotting)- ProliferationPlasma (Prepared by centrifugation, no clotting)- no proliferation

Clottingallows platelets to release secretory granulesPlatelet-derived growth factor (PDGF)

Connective tissue cells express PDGF receptors which bind the small PDGF glycoprotein

Other Growth FactorsInterleukin-2 (IL-2)

Stimulates T lymphocytesNerve Growth Factor (NGF)

Promotes neuronal survival and growthEpidermal Growth Factor (EGF)Vascular Endothelial Growth Factor (VEGF)Insulin-like growth factors (IFG-1, IGF-2)

Cell Cycle- Internal Regulators1980s - studies in Xenopus eggs and starfish oocytes: purification of M phase-promoting factor(MPF); identification of its components as cyclin B and CDC2 (also called cyclin-dependentkinase, Cell Division Cycle)

(/cellbiology/index.php/File:PRB_E2F_interaction2.jpg)Cyclin D Interactions

CyclinsCyclins are synthesized and degraded each cell cycle (hence the name)

Cyclins and Cyclin-Dependent Kinases need to interact for cell cycle progression Cyclins andCyclin-Dependent Kinases (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.3200)

(/cellbiology/index.php/File:Cell_cycle1.jpg)

Cyclin Dcyclin D1, D2 and D3expression induced by growth factors stimulation

serum growth factors to quiescent cellspromotes transcription of the cyclin D1 gene

Cyclin D1 then binds Cdk4 and Cdk6 in early tomid-G1 phase

phosphorylate and inactivate retinoblastomaprotein (pRb)

also acts as a cofactor for several transcriptionfactors in numerous cell types

Cyclin D1 is a proto-oncogene

proto-oncogene - a normal gene that can becomean oncogene due to mutations or increasedexpression.mutations are associated with cancer progression

as a regulator of G1 to S-phase transition

Cyclin Erequired for transition from G1 to S phaseCyclin E binds to G1 phase Cdk2Cyclin E/Cdk2 complex phosphorylates p27Kip1 which then degrades

an inhibitor of Cyclin Dactivation of Cyclin E gene can be blocked by the cdk inhibitor p16 (Cyclin-dependent kinaseinhibitor 2A)

tumor suppressor proteinexpression of Cyclin A then increases for progress to S phase

Cdk/cyclin complexes (http://dev.biologists.org/content/140/15/3079/F2.expansion.html)

Cyclin Aaccumulates from early S phase

role not fully understood, required for S phase progressCyclin A binds Cdk2disappears ahead of cyclin B during mitosiscan bind to both Cdc2 and Cdk2

Cyclin Baccumulates from S phaseCyclin B forms a complex with Cdc2

complex is kept inactive by phosphorylation of Cdc2abruptly activated by Cdc25 during mitosis

cyclin B is destroyed at mitosis exit by ubiquitin-mediated mechanism (catalyzed by theAPC/C)

Anaphase-Promoting Complex (APC, cyclosome, APC/C)

degrades the mitotic (B) cyclinstriggers the events leading to destruction of the cohesinsallowing the sister chromatids to separate

cyclinB-GFP (http://movie.rupress.org/video/10.1083/jcb.200203035/video-5)

Links: MBC Figure 13-2. Current model for regulation of the eukaryotic cell cycle(http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A3463&rendertype=figure&id=A3467) | control of proteolysis by SCF and APCduring the cell cycle (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.3211The)

Cyclin-dependent KinasesInactive until bound to a specific cyclinkinase - means an enzyme which phosphorylates a target protein(s)Drive M to S Phase

cdk1 and cdk2

(/cellbiology/index.php/File:Cell_cycle_-_Cdk_cyclin.jpg)Cell cycle - Cdk cyclins

Cdk1 activated at G2 to Munphosphorylated Cdk1 increases asa function of cell size in the G2 phase(mechanism that regulates cell size inanimal cells) PMID 23316440

Cdk2 activated at G1 to Snuclear proteins and proteins involved inregulating metabolic processes

phosphorylated (inactivated) by CDK1or CDK2 in mitotic cells. PMID20068231

Movie CDK/Cyclin: Cell-Cycle Control

(http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/mcb/ch24anim1.mov)

Cell Cyclin ChangesInterphase and M Phase

Division controlled by synthesis/degradation cyclin Bregulatory subunit of Cdc2 protein kinaseinterphase cyclin B synthesis leads to formation of active cyclin B–Cdc2 complexinduces entry into mitosis

Rapid degradation of cyclin B leads to inactivation Cdc2 kinase

Allow cell to exit mitosis and return to interphase next cell cycle

cyclin B-CDC2 acts as M phase-promoting factor (MPF)activate other proteins through phosphorylation

cyclin A down-regulation induces a G2 phase arrest through a checkpoint-independentinactivation of cyclin B-CDC2 by inhibitory phosphorylation.

cyclin A cannot form MPF independent of cyclin B

Regulator CheckpointsThese regulators are often described as "tumor suppressor proteins" due to their ability to blocktumor (cancer) growth. Conversely, mutations in these genes often lead to tumor growth.

Checkpoints in the cell-cycle control system (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.3197)

How DNA damage arrests the cell cycle in G1 (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.3241)

Multiple checkpoints control cell cycle progression(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667593/figure/F2/)

(/cellbiology/index.php/File:P53_pathways.jpg)p53 pathways

p53(TP53) A multifunctional protein Mr 53 kDaregulating cell cycle and apoptosisAs a cell cycle regulator it recognizes andbinds damaged DNA

single-stranded DNA,insertion/deletion mismatches, andfree DNA ends

Acts as a transcription factor activatingp21 transcription

p21 protein then inhibits G1 cyclin-dependent kinases p21

(http://www.landesbioscience.com/curie/chapter/4236)p53-induced cell-cycle arrest in response to DNA damage(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mcb.figgrp.3583)

unstressed cells

p53 levels are low through a continuous degradationMdm2 (HDM2 in humans)

binds p53blocks actiontransports p53 from nucleus to the cytosol

gene has been shown to be damaged in cells by mutagensmutations found with

Li-Fraumeni syndrome OMIM 151623 (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=151623)

Effect of mutation of the p53 tumorsuppressor gene on G1 DNA-damage checkpoint control(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mcb.figgrp.3582)

Science magazine designated p53 the 'Molecule of the Year' for 1993

pRbretinoblastoma protein regulating cell cycleAs a cell cycle regulator it recognizes damaged DNA

restricts cell ability to replicate DNA by preventing its progression from the G1 to Sbinds and inhibits transcription factors of the E2F family

active pRb is hypophosphorylatedinactive pRb is phosphorylated

(/cellbiology/index.php/File:Cancer_requires_multiple_mutations.png)Cancer requiresmultiple mutations

(/cellbiology/index.php/File:PRB_E2F_interaction2.jpg)pRb Interactions

mutations in this gene lead to the diseaseretinoblastoma OMIM 180200(http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=180200)

p16Restriction point control(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mcb.figgrp.7144)

also called Cyclin-dependent kinase inhibitor 2Ablocks activation of Cyclin E genemutations found with

pancreatic adenocarcinoma OMIM 260350(http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=260350)esophageal and gastric cancer cell lines

Oncogenesis

MH - There are many detailed resources on oncogenesis (cancer) thisis only a brief mention in regard to cell cycle. See also the tumorsuppressor section above. An important issue is the concept of"multiple hits".

some viruses can infect human cells and lead to oncogenesis(cervical cancer, liver cancer, and certain lymphomas, leukemias,and sarcomas)

for example - human papillomavirus (HPV)

(/cellbiology/index.php/File:Leukaemia_deregulated_cell_cycle_check_point_proteins.jpg)

Cell cycle phases showing some of the check point proteins that can be deregulated inleukaemia.

Stem CellsExample of Cell cycle regulation in hematopoietic stem cells (HSCs). PMID 22123859

Distinct cell cycle activity in fetal, adult, and old HSCs(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257565/figure/fig1/)HSC cell cycle entry is regulated by a complex network of cell-intrinsic and cell-extrinsicfactors. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257565/figure/fig2)

Additional InformationThe following recent research is not examinable.

Intrinsic and extrinsic mechanisms regulating satellitecell functionDevelopment. 2015 May 1;142(9):1572-1581. Review

Dumont NA1, Wang YX2, Rudnicki MA3.

Abstract Muscle stem cells, termed satellite cells, are crucial for skeletal muscle growth andregeneration. In healthy adult muscle, satellite cells are quiescent but poised for activation. Duringmuscle regeneration, activated satellite cells transiently re-enter the cell cycle to proliferate andsubsequently exit the cell cycle to differentiate or self-renew. Recent studies have demonstrated

that satellite cells are heterogeneous and that subpopulations of satellite stem cells are able toperform asymmetric divisions to generate myogenic progenitors or symmetric divisions to expandthe satellite cell pool. Thus, a complex balance between extrinsic cues and intrinsic regulatorymechanisms is needed to tightly control satellite cell cycle progression and cell fatedetermination. Defects in satellite cell regulation or in their niche, as observed in degenerativeconditions such as aging, can impair muscle regeneration. Here, we review recent discoveries ofthe intrinsic and extrinsic factors that regulate satellite cell behaviour in regenerating anddegenerating muscles. © 2015. Published by The Company of Biologists Ltd. KEYWORDS:Aging; Asymmetric division; Cell cycle regulation; Muscle stem cell; Myogenesis; Quiescence;Regeneration; Satellite cell; Self-renewal; Skeletal muscle PMID 25922523

http://dev.biologists.org/content/142/9/1572.long(http://dev.biologists.org/content/142/9/1572.long)

Regulation of the cell cycle in satellite cells.

http://dev.biologists.org/content/142/9/1572/F2.expansion.html(http://dev.biologists.org/content/142/9/1572/F2.expansion.html)

Cdks, cyclins and CKIs: roles beyond cell cycleregulationDevelopment. 2013 Aug;140(15):3079-93. doi: 10.1242/dev.091744.

Lim S1, Kaldis P.

Abstract

Cyclin-dependent kinases (Cdks) are serine/threonine kinases and their catalytic activities aremodulated by interactions with cyclins and Cdk inhibitors (CKIs). Close cooperation between thistrio is necessary for ensuring orderly progression through the cell cycle. In addition to their well-established function in cell cycle control, it is becoming increasingly apparent that mammalianCdks, cyclins and CKIs play indispensable roles in processes such as transcription, epigeneticregulation, metabolism, stem cell self-renewal, neuronal functions and spermatogenesis. Evenmore remarkably, they can accomplish some of these tasks individually, without the need forCdk/cyclin complex formation or kinase activity. In this Review, we discuss the latest revelationsabout Cdks, cyclins and CKIs with the goal of showcasing their functional diversity beyond cellcycle regulation and their impact on development and disease in mammals.

PMID 23861057 Development (http://dev.biologists.org/content/140/15/3079.long)

Connecting the nucleolus to the cell cycle and humandiseaseFASEB J. 2014 Apr 30. [Epub ahead of print]

Tsai RY1, Pederson T.

Abstract

Long known as the center of ribosome synthesis, the nucleolus is connected to cell cycleregulation in more subtle ways. One is a surveillance system that reacts promptly when rRNAsynthesis or processing is impaired, halting cell cycle progression. Conversely, the nucleolus alsoacts as a first-responder to growth-related stress signals. Here we review emerging concepts onhow these "infraribosomal" links between the nucleolus and cell cycle progression operate in bothforward and reverse gears. We offer perspectives on how new cancer therapeutic designs thattarget this infraribosomal mode of cell growth control may shape future clinical progress.

PMID 24790035

p53 and ribosome biogenesis stress: The essentialsFEBS Lett. 2014 Apr 18. pii: S0014-5793(14)00300-7. doi: 10.1016/j.febslet.2014.04.014. [Epubahead of print]

Golomb L1, Volarevic S2, Oren M3.

Abstract

Cell proliferation and cell growth are two tightly linked processes, as the proliferation programcannot be executed without proper accumulation of cell mass, otherwise endangering the fate ofthe two daughter cells. It is therefore not surprising that ribosome biogenesis, a key element incell growth, is regulated by many cell cycle regulators. This regulation is exerted transcriptionallyand post-transcriptionally, in conjunction with numerous intrinsic and extrinsic signals. Thosesignals eventually converge at the nucleolus, the cellular compartment that is not only responsiblefor executing the ribosome biogenesis program, but also serves as a regulatory hub, responsiblefor integrating and transmitting multiple stress signals to the omnipotent cell fate gatekeeper, p53.In this review we discuss when, how and why p53 is activated upon ribosomal biogenesis stress,and how perturbation of this critical regulatory interplay may impact human disease. Copyright ©2014. Published by Elsevier B.V.

PMID 24747423

ReferencesTextbooksEssential Cell Biology

Essential Cell Biology Chapter 17

Molecular Biology of the CellAlberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter NewYork and London: Garland Science; c2002

Molecular Biology of the Cell 4th ed. - IV. Internal Organization of the Cell Chapter 17. TheCell Cycle and Programmed Cell DeathAn Overview of the Cell Cycle (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.section.3169)Figure 17-1. The cell cycle (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.figgrp.3168)The Cell Cycle and Programmed Cell Death (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?

db=Books&rid=mboc4.chapter.3167)

Molecular Cell BiologyLodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell,James E. New York: W. H. Freeman & Co.; c1999

Molecular Cell Biology - Chapter 13. Regulation of the Eukaryotic Cell CycleRegulation of the Eukaryotic Cell Cycle (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.chapter.3432)Overview of the Cell Cycle and Its Control (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.section.3463)Figure 13-2. Current model for regulation of the eukaryotic cell cycle(http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.figgrp.3467)Movie: Cell Cycle Control(http://www.ncbi.nlm.nih.gov:80/books/bookres.fcgi/mcb/ch13anim1.mov)

The Cell- A Molecular ApproachCooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

The Cell - A Molecular Approach - IV. Cell Regulation Chapter 14. The Cell CycleThe Eukaryotic Cell Cycle (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.section.2433)Figure 14.1. Phases of the cell cycle (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.figgrp.2435)

Search Online Textbooks"cell cycle" Molecular Biology of the Cell (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=cell+cycle+mboc4) | Molecular Cell Biology(http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=cell+cycle+mcb) |The Cell- A molecular Approach (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=cell+cycle+cooper) | Bookshelf(http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=cell+cycle)"cyclin" Molecular Biology of the Cell (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=cyclin+mboc4) | Molecular Cell Biology(http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=cyclin+mcb) | TheCell- A molecular Approach (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=cyclin+cooper) | Bookshelf(http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=cyclin)

Books

PubMedPubMed is a service of the U.S. National Library of Medicine that includes over 18 millioncitations from MEDLINE and other life science journals for biomedical articles back to 1948.PubMed includes links to full text articles and other related resources. PubMed(http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed)PubMed Central (PMC) is a free digital archive of biomedical and life sciences journalliterature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine

(NLM) allowing all users free access to the material in PubMed Central. PMC(http://www.ncbi.nlm.nih.gov/sites/entrez?db=PMC)Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of humangenes and genetic phenotypes. The full-text, referenced overviews in OMIM containinformation on all known mendelian disorders and over 12,000 genes. OMIM(http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim)Entrez is the integrated, text-based search and retrieval system used at NCBI for the majordatabases, including PubMed, Nucleotide and Protein Sequences, Protein Structures,Complete Genomes, Taxonomy, and others Entrez(http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar)

Search Pubmed"cell cycle" Entrez all databases (http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=cell+cycle)"cyclin" Entrez all databases (http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=cyclin)"cyclin dependent kinase" Entrez all databases (http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=cyclin+dependent+kinase)"p53" Entrez all databases (http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=p53)"pRb" Entrez all databases (http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=pRb)

ReviewsThe great divide: coordinating cell cycle events during bacterial growth and division.Haeusser DP, Levin PA. Curr Opin Microbiol. 2008 Apr;11(2):94-9. Epub 2008 Apr 7. Review.PMID 18396093 | PMC (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18396093)Cell cycle studies based upon quantitative image analysis. Stacey DW, Hitomi M. CytometryA. 2008 Apr;73(4):270-8. Review PMID 18163464Analysis of cell cycle phases and progression in cultured mammalian cells. Schorl C, SedivyJM. Methods. 2007 Feb;41(2):143-50. Review. PMID 17189856Cell cycle regulation of DNA replication. Sclafani RA, Holzen TM. Annu Rev Genet.2007;41:237-80. Review. PMID 17630848

OMIMTP53 OMIM 191170 (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170)

External LinksNature Cell Division (http://www.nature.com/celldivision/index.html) | Cell Division Milestones(http://www.nature.com/celldivision/milestones/index.html)MCB Figure 13-2Current model for regulation of the eukaryotic cell cycle(https://www.ncbi.nlm.nih.gov/books/NBK21466/figure/A3467/?report=objectonly) | CellCycle Movie(/cellbiology/images/6/68/MCB_Overview_of_the_Cell_Cycle_and_Its_Control.mp4)

Movies

(http://moodle.telt.unsw.edu.au/course/view.php?id=25143)Moodle

Journal of Visualized Experiments (JoVE)Temporal Tracking of Cell Cycle Progression Using Flow Cytometry without the Need forSynchronization (http://www.jove.com/video/52840/temporal-tracking-cell-cycle-progression-using-flow-cytometry-without)Measuring Cell Cycle Progression Kinetics with Metabolic Labeling and Flow Cytometry(http://www.jove.com/video/4045/measuring-cell-cycle-progression-kinetics-with-metabolic-labeling)

Fzy and Fzr cooperate to destroy cyclin B in flies Raff et al.(http://jcb.rupress.org/cgi/content/abstract/157/7/1139) examine two regulators of fly cyclin Bdestruction (http://jcb.rupress.org/cgi/content/full/jcb.200203035/DC1/5): Fizzy (Fzy)/Cdc20and Fzy-related (Fzr)/Cdh1. Fzy/Cdc20(http://jcb.rupress.org/cgi/content/full/jcb.200203035/DC1/1) is concentrated at kinetochoresand centrosomes early in mitosis, whereas Fzr/Cdh1(http://jcb.rupress.org/cgi/content/full/jcb.200203035/DC1/2) is concentrated at centrosomesthroughout the cell cycle. In syncytial embryos, only Fzy/Cdc20 is present, and only thespindle-associated cyclin B is degraded at the end of mitosis. A mutant form of cyclin B thatcannot be targeted for destruction by Fzy/Cdc20 is no longer degraded on spindles ofsyncytial embryos (http://jcb.rupress.org/cgi/content/full/jcb.200203035/DC1/6), but stilltargeted by Fzr/Cdh1 in cellularized embryos(http://jcb.rupress.org/cgi/content/full/jcb.200203035/DC1/7), albeit more slowly than normal.This suggest that Fzy/Cdc20 is responsible for catalyzing the first phase of cyclin Bdestruction that occurs on the mitotic spindle, whereas Fzr/Cdh1 is responsible for catalyzingthe second phase of cyclin B destruction that occurs throughout the cell.Jove - Cell Cycle (http://www.jove.com/keyword/cell+cycle) - Analysis of Cell Cycle Positionin Mammalian Cells (http://www.jove.com/video/3491/analysis-of-cell-cycle-position-in-mammalian-cells)

2017 Course ContentLectures: Cell Biology Introduction(/cellbiology/index.php/Cell_Biology_Introduction) | Cells Eukaryotes andProkaryotes (/cellbiology/index.php/Cells_Eukaryotes_and_Prokaryotes) | CellMembranes and Compartments(/cellbiology/index.php/Cell_Membranes_and_Compartments) | Cell Nucleus(/cellbiology/index.php/Cell_Nucleus) | Cell Export - Exocytosis(/cellbiology/index.php/Cell_Export_-_Exocytosis) | Cell Import - Endocytosis(/cellbiology/index.php/Cell_Import_-_Endocytosis) | CytoskeletonIntroduction (/cellbiology/index.php/Cytoskeleton_Introduction) | Cytoskeleton- Microfilaments (/cellbiology/index.php/Cytoskeleton_-_Microfilaments) | Cytoskeleton -Microtubules (/cellbiology/index.php/Cytoskeleton_-_Microtubules) | Cytoskeleton - IntermediateFilaments (/cellbiology/index.php/Cytoskeleton_-_Intermediate_Filaments) | Cell Mitochondria(/cellbiology/index.php/Cell_Mitochondria) | Cell Junctions (/cellbiology/index.php/Cell_Junctions)| Extracellular Matrix 1 (/cellbiology/index.php/Extracellular_Matrix_1) | Extracellular Matrix 2(/cellbiology/index.php/Extracellular_Matrix_2) | Cell Cycle | Cell Division

(/cellbiology/index.php/Cell_Division) | Cell Death 1 (/cellbiology/index.php/Cell_Death_1) | CellDeath 2 (/cellbiology/index.php/Cell_Death_2) | Signal 1 (/cellbiology/index.php/Signal_1) | Signal2 (/cellbiology/index.php/Signal_2) | Stem Cells 1 (/cellbiology/index.php/Stem_Cells_1) | StemCells 2 (/cellbiology/index.php/Stem_Cells_2) | Development(/cellbiology/index.php/Development) | 2017 Revision (/cellbiology/index.php/2017_Revision)

2017 Laboratories: Introduction to Lab (/cellbiology/index.php/2017_Lab_1) | Fixation andStaining (/cellbiology/index.php/2017_Lab_2) |

2017 Projects (/cellbiology/index.php/ANAT3231_Projects_2017): Group 1 - Delta(/cellbiology/index.php/2017_Group_1_Project) | Group 2 - Duct(/cellbiology/index.php/2017_Group_2_Project) | Group 3 - Beta(/cellbiology/index.php/2017_Group_3_Project) | Group 4 - Alpha(/cellbiology/index.php/2017_Group_4_Project)

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G

Categories (/cellbiology/index.php/Special:Categories): Science-Undergraduate (/cellbiology/index.php/Category:Science-Undergraduate)2017ANAT3231 (/cellbiology/index.php/Category:2017ANAT3231)

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