SlideShare a Scribd company logo
1 of 67
Chromosomes and Mitosis Lecture 6
1 Chromosomal Basis of Heredity ,[object Object],[object Object],[object Object]
Chromosomes replicate during cell division
The chromosome complement
Chromosome analysis Cri Du Chat results from loss of a small piece of chromosome 5
Gene Map
Chromosome pairs
Non-identical genes
Sex chromosomes ,[object Object],[object Object],[object Object]
Two types of Cell Division ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],46 46  46 46 23  23  23  23
The Cell Cycle
S phase Replication Condensation Schematic
DNA replication  Duplex DNA begins Replicating Replication bubbles merge creating two duplexes
Mitosis
The stages of Mitosis
Prophase Detail
Prometaphase
Metaphase
Anaphase
Telophase
The sum total of the process
Karyotypes
Chromosome Length
Chromosome appearance
Meiosis and Gametogenesis
Somatic and Germline cells ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Meiosis
Meiosis is required for gametogenesis
Meiosis I Somatic cells Germline Cells
Interphase I and Prophase I Leptotene
Prophase I Zygotene
Prophase I Pachytene
Prophase I Diplotene
Recombination
And on the molecular level
Metaphase I and anaphase I
Meiosis I is the reduction division
Non-disjunction
Telophase I
Cytokinesis sperm formation oocyte formation
Meiosis II
A comparison of meiosis and mitosis Germline Somatic Cells involved 4 2 Cells resulting 2 1 Nuclear Divisions Reduces  Maintains Chromosome number Meiosis Mitosis
Relationship to Gametogenesis
Sperm and Egg formation
Gametogenesis
Fertilization ,[object Object],[object Object],[object Object]
Mitotic Non-disjunction
Cell cycle and apoptosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Control of entry into cell cycle and apoptosis ,[object Object],[object Object],[object Object]
Cyclins and CDK’s ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cyclins bind CDK’s ,[object Object],[object Object],[object Object],[object Object],[object Object]
The exit from Go ,[object Object],[object Object],[object Object]
Events during G1 ,[object Object],[object Object],[object Object]
G1/S checkpoint ,[object Object],[object Object],[object Object],[object Object],[object Object]
And those genes are ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Other Checkpoints ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Downregulation of cyclin influenced CDK activity ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
MPF activates APC which ubiquitinates cyclin B
In the overall ,[object Object],[object Object],[object Object],[object Object],[object Object]
Apoptosis  (apo – toe – sis) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
The apoptotic cell ,[object Object],[object Object],[object Object],[object Object],[object Object]
The mechanisms of apotosis ,[object Object],[object Object],[object Object],[object Object]
P53 controls entry into S-phase ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
But if the DNA damage is extensive ,[object Object],[object Object],[object Object],[object Object],[object Object]
The caspases ,[object Object],[object Object],[object Object],[object Object]
External apoptotic mechanisms ,[object Object],[object Object],[object Object],[object Object]
Fas/Fas ligand signaling ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

More Related Content

What's hot

Cell cycle presentation by Salman Ul Islam.
Cell cycle presentation by Salman Ul Islam.Cell cycle presentation by Salman Ul Islam.
Cell cycle presentation by Salman Ul Islam.
Salman Ul Islam
 
molecular mechanisms in cell division
molecular mechanisms in cell divisionmolecular mechanisms in cell division
molecular mechanisms in cell division
Dr-HAMDAN
 
Power Point Cell Cycle & Apoptosis
Power Point Cell Cycle & ApoptosisPower Point Cell Cycle & Apoptosis
Power Point Cell Cycle & Apoptosis
Firdika Arini
 

What's hot (19)

cell cycle
cell cyclecell cycle
cell cycle
 
Cell cycle
Cell cycleCell cycle
Cell cycle
 
Cell cycle
Cell cycleCell cycle
Cell cycle
 
Cell cycle and regulation
Cell cycle and regulation Cell cycle and regulation
Cell cycle and regulation
 
Cell cycle
Cell cycleCell cycle
Cell cycle
 
Cell cycle and control of cell division.
Cell cycle and control of cell division.Cell cycle and control of cell division.
Cell cycle and control of cell division.
 
Cell cycle
Cell cycleCell cycle
Cell cycle
 
Cell cycle (Without Mieosis)
Cell cycle (Without Mieosis)Cell cycle (Without Mieosis)
Cell cycle (Without Mieosis)
 
Cell cycle presentation by Salman Ul Islam.
Cell cycle presentation by Salman Ul Islam.Cell cycle presentation by Salman Ul Islam.
Cell cycle presentation by Salman Ul Islam.
 
Cel cycle and its regulation
Cel cycle and its regulationCel cycle and its regulation
Cel cycle and its regulation
 
Cell cycle
Cell cycleCell cycle
Cell cycle
 
Cell cycle
Cell cycleCell cycle
Cell cycle
 
molecular mechanisms in cell division
molecular mechanisms in cell divisionmolecular mechanisms in cell division
molecular mechanisms in cell division
 
13.cell cycle -A- cell biology
13.cell cycle -A- cell biology13.cell cycle -A- cell biology
13.cell cycle -A- cell biology
 
Cell Cycle Regulation
Cell Cycle RegulationCell Cycle Regulation
Cell Cycle Regulation
 
The cell cycle
The cell cycleThe cell cycle
The cell cycle
 
Power Point Cell Cycle & Apoptosis
Power Point Cell Cycle & ApoptosisPower Point Cell Cycle & Apoptosis
Power Point Cell Cycle & Apoptosis
 
Cell cycle
Cell cycleCell cycle
Cell cycle
 
Cell cycle regulation ppt
Cell cycle regulation  pptCell cycle regulation  ppt
Cell cycle regulation ppt
 

Viewers also liked (8)

MolBiol #3.2
MolBiol #3.2MolBiol #3.2
MolBiol #3.2
 
Molbiol 2011-08-epigenetics
Molbiol 2011-08-epigeneticsMolbiol 2011-08-epigenetics
Molbiol 2011-08-epigenetics
 
Guests 2011-10-04-pevzner-rearrangements
Guests 2011-10-04-pevzner-rearrangementsGuests 2011-10-04-pevzner-rearrangements
Guests 2011-10-04-pevzner-rearrangements
 
Biotech 2011-05-eukaryotic-genes
Biotech 2011-05-eukaryotic-genesBiotech 2011-05-eukaryotic-genes
Biotech 2011-05-eukaryotic-genes
 
MolBiol #4.2
MolBiol #4.2MolBiol #4.2
MolBiol #4.2
 
Molbiol 2011-06-transcription-translation
Molbiol 2011-06-transcription-translationMolbiol 2011-06-transcription-translation
Molbiol 2011-06-transcription-translation
 
BioTech #5
BioTech #5BioTech #5
BioTech #5
 
Assembly and finishing
Assembly and finishingAssembly and finishing
Assembly and finishing
 

Similar to Molbiol 2011-07-chromosomes-cell-cycle

Introduction to the cell cycle
Introduction to the cell cycleIntroduction to the cell cycle
Introduction to the cell cycle
Elsa von Licy
 
Cell Cycle and Its Control Mechanism : Devendra Kumar
Cell Cycle and Its Control Mechanism : Devendra KumarCell Cycle and Its Control Mechanism : Devendra Kumar
Cell Cycle and Its Control Mechanism : Devendra Kumar
Devendra Kumar
 

Similar to Molbiol 2011-07-chromosomes-cell-cycle (20)

Oncogenesis in Neurosurgery.pptx
Oncogenesis in Neurosurgery.pptxOncogenesis in Neurosurgery.pptx
Oncogenesis in Neurosurgery.pptx
 
Cell cycle and cell division
Cell cycle and cell divisionCell cycle and cell division
Cell cycle and cell division
 
Cell cycle and growth regulation
Cell cycle and growth regulation Cell cycle and growth regulation
Cell cycle and growth regulation
 
cell biology by dr bekhet elkott
cell biology by dr bekhet elkottcell biology by dr bekhet elkott
cell biology by dr bekhet elkott
 
Mitosis
MitosisMitosis
Mitosis
 
Cell cycle and apoptosis
Cell cycle and apoptosisCell cycle and apoptosis
Cell cycle and apoptosis
 
Cell cycle and molecular basis of cancer.
Cell cycle and molecular basis of cancer.Cell cycle and molecular basis of cancer.
Cell cycle and molecular basis of cancer.
 
Introduction to the cell cycle
Introduction to the cell cycleIntroduction to the cell cycle
Introduction to the cell cycle
 
Cell cycle and its regulation . topic from essential of genetics.pptx
Cell cycle and its regulation . topic from essential of genetics.pptxCell cycle and its regulation . topic from essential of genetics.pptx
Cell cycle and its regulation . topic from essential of genetics.pptx
 
Cell cycle
Cell cycleCell cycle
Cell cycle
 
CELL CYCLE & ITS REGULATION.pptx
CELL CYCLE & ITS REGULATION.pptxCELL CYCLE & ITS REGULATION.pptx
CELL CYCLE & ITS REGULATION.pptx
 
Biology of cancer
Biology of cancerBiology of cancer
Biology of cancer
 
Cell Cycle and Its Control Mechanism : Devendra Kumar
Cell Cycle and Its Control Mechanism : Devendra KumarCell Cycle and Its Control Mechanism : Devendra Kumar
Cell Cycle and Its Control Mechanism : Devendra Kumar
 
AP Bio Ch11 PowerPoint
 AP Bio Ch11 PowerPoint AP Bio Ch11 PowerPoint
AP Bio Ch11 PowerPoint
 
Cell Cycle- an essential part of cell growth
Cell Cycle- an essential part of cell growthCell Cycle- an essential part of cell growth
Cell Cycle- an essential part of cell growth
 
Cell Cycle
Cell CycleCell Cycle
Cell Cycle
 
The cell cycle by Sami
The cell cycle by SamiThe cell cycle by Sami
The cell cycle by Sami
 
Cell cycle and mitosis presentation (3)
Cell cycle and mitosis presentation (3)Cell cycle and mitosis presentation (3)
Cell cycle and mitosis presentation (3)
 
Presentation 01 - The Cell Cycle
Presentation 01 - The Cell CyclePresentation 01 - The Cell Cycle
Presentation 01 - The Cell Cycle
 
1. CELL DIVISION.pptx
1. CELL DIVISION.pptx1. CELL DIVISION.pptx
1. CELL DIVISION.pptx
 

More from Nikolay Vyahhi

Molbiol 2011-13-organelles
Molbiol 2011-13-organellesMolbiol 2011-13-organelles
Molbiol 2011-13-organelles
Nikolay Vyahhi
 
Molbiol 2011-12-eukaryotic gene-expression
Molbiol 2011-12-eukaryotic gene-expressionMolbiol 2011-12-eukaryotic gene-expression
Molbiol 2011-12-eukaryotic gene-expression
Nikolay Vyahhi
 
Molbiol 2011-10-proteins
Molbiol 2011-10-proteinsMolbiol 2011-10-proteins
Molbiol 2011-10-proteins
Nikolay Vyahhi
 
Molbiol 2011-09-reparation-recombination
Molbiol 2011-09-reparation-recombinationMolbiol 2011-09-reparation-recombination
Molbiol 2011-09-reparation-recombination
Nikolay Vyahhi
 
Molbiol 2011-08-epigenetics
Molbiol 2011-08-epigeneticsMolbiol 2011-08-epigenetics
Molbiol 2011-08-epigenetics
Nikolay Vyahhi
 
Molbiol 2011-07-chromosomes-cell-cycle
Molbiol 2011-07-chromosomes-cell-cycleMolbiol 2011-07-chromosomes-cell-cycle
Molbiol 2011-07-chromosomes-cell-cycle
Nikolay Vyahhi
 
Molbiol 2011-05-dna-rna-protein
Molbiol 2011-05-dna-rna-proteinMolbiol 2011-05-dna-rna-protein
Molbiol 2011-05-dna-rna-protein
Nikolay Vyahhi
 
Molbiol 2011-04-metabolism
Molbiol 2011-04-metabolismMolbiol 2011-04-metabolism
Molbiol 2011-04-metabolism
Nikolay Vyahhi
 
Molbiol 2011-03-biochem
Molbiol 2011-03-biochemMolbiol 2011-03-biochem
Molbiol 2011-03-biochem
Nikolay Vyahhi
 
Molbiol 2011-02-biology
Molbiol 2011-02-biologyMolbiol 2011-02-biology
Molbiol 2011-02-biology
Nikolay Vyahhi
 
Molbiol 2011-01-chemistry
Molbiol 2011-01-chemistryMolbiol 2011-01-chemistry
Molbiol 2011-01-chemistry
Nikolay Vyahhi
 
Molbiol 2011-11-role of-proteins
Molbiol 2011-11-role of-proteinsMolbiol 2011-11-role of-proteins
Molbiol 2011-11-role of-proteins
Nikolay Vyahhi
 
Biotech 2011-08-recombinant-dna
Biotech 2011-08-recombinant-dnaBiotech 2011-08-recombinant-dna
Biotech 2011-08-recombinant-dna
Nikolay Vyahhi
 
Biotech 2011-02-genetics
Biotech 2011-02-geneticsBiotech 2011-02-genetics
Biotech 2011-02-genetics
Nikolay Vyahhi
 
Biotech 2011-10-methods
Biotech 2011-10-methodsBiotech 2011-10-methods
Biotech 2011-10-methods
Nikolay Vyahhi
 
Biotech 2011-09-pcr and-in_situ_methods
Biotech 2011-09-pcr and-in_situ_methodsBiotech 2011-09-pcr and-in_situ_methods
Biotech 2011-09-pcr and-in_situ_methods
Nikolay Vyahhi
 
Biotech 2011-07-finding-orf-etc
Biotech 2011-07-finding-orf-etcBiotech 2011-07-finding-orf-etc
Biotech 2011-07-finding-orf-etc
Nikolay Vyahhi
 
Biotech 2011-06-electrophoresis-blots
Biotech 2011-06-electrophoresis-blotsBiotech 2011-06-electrophoresis-blots
Biotech 2011-06-electrophoresis-blots
Nikolay Vyahhi
 
Biotech 2011-05-eukaryotic-genes
Biotech 2011-05-eukaryotic-genesBiotech 2011-05-eukaryotic-genes
Biotech 2011-05-eukaryotic-genes
Nikolay Vyahhi
 

More from Nikolay Vyahhi (20)

Molbiol 2011-wetlab
Molbiol 2011-wetlabMolbiol 2011-wetlab
Molbiol 2011-wetlab
 
Molbiol 2011-13-organelles
Molbiol 2011-13-organellesMolbiol 2011-13-organelles
Molbiol 2011-13-organelles
 
Molbiol 2011-12-eukaryotic gene-expression
Molbiol 2011-12-eukaryotic gene-expressionMolbiol 2011-12-eukaryotic gene-expression
Molbiol 2011-12-eukaryotic gene-expression
 
Molbiol 2011-10-proteins
Molbiol 2011-10-proteinsMolbiol 2011-10-proteins
Molbiol 2011-10-proteins
 
Molbiol 2011-09-reparation-recombination
Molbiol 2011-09-reparation-recombinationMolbiol 2011-09-reparation-recombination
Molbiol 2011-09-reparation-recombination
 
Molbiol 2011-08-epigenetics
Molbiol 2011-08-epigeneticsMolbiol 2011-08-epigenetics
Molbiol 2011-08-epigenetics
 
Molbiol 2011-07-chromosomes-cell-cycle
Molbiol 2011-07-chromosomes-cell-cycleMolbiol 2011-07-chromosomes-cell-cycle
Molbiol 2011-07-chromosomes-cell-cycle
 
Molbiol 2011-05-dna-rna-protein
Molbiol 2011-05-dna-rna-proteinMolbiol 2011-05-dna-rna-protein
Molbiol 2011-05-dna-rna-protein
 
Molbiol 2011-04-metabolism
Molbiol 2011-04-metabolismMolbiol 2011-04-metabolism
Molbiol 2011-04-metabolism
 
Molbiol 2011-03-biochem
Molbiol 2011-03-biochemMolbiol 2011-03-biochem
Molbiol 2011-03-biochem
 
Molbiol 2011-02-biology
Molbiol 2011-02-biologyMolbiol 2011-02-biology
Molbiol 2011-02-biology
 
Molbiol 2011-01-chemistry
Molbiol 2011-01-chemistryMolbiol 2011-01-chemistry
Molbiol 2011-01-chemistry
 
Molbiol 2011-11-role of-proteins
Molbiol 2011-11-role of-proteinsMolbiol 2011-11-role of-proteins
Molbiol 2011-11-role of-proteins
 
Biotech 2011-08-recombinant-dna
Biotech 2011-08-recombinant-dnaBiotech 2011-08-recombinant-dna
Biotech 2011-08-recombinant-dna
 
Biotech 2011-02-genetics
Biotech 2011-02-geneticsBiotech 2011-02-genetics
Biotech 2011-02-genetics
 
Biotech 2011-10-methods
Biotech 2011-10-methodsBiotech 2011-10-methods
Biotech 2011-10-methods
 
Biotech 2011-09-pcr and-in_situ_methods
Biotech 2011-09-pcr and-in_situ_methodsBiotech 2011-09-pcr and-in_situ_methods
Biotech 2011-09-pcr and-in_situ_methods
 
Biotech 2011-07-finding-orf-etc
Biotech 2011-07-finding-orf-etcBiotech 2011-07-finding-orf-etc
Biotech 2011-07-finding-orf-etc
 
Biotech 2011-06-electrophoresis-blots
Biotech 2011-06-electrophoresis-blotsBiotech 2011-06-electrophoresis-blots
Biotech 2011-06-electrophoresis-blots
 
Biotech 2011-05-eukaryotic-genes
Biotech 2011-05-eukaryotic-genesBiotech 2011-05-eukaryotic-genes
Biotech 2011-05-eukaryotic-genes
 

Recently uploaded

Why Teams call analytics are critical to your entire business
Why Teams call analytics are critical to your entire businessWhy Teams call analytics are critical to your entire business
Why Teams call analytics are critical to your entire business
panagenda
 
Architecting Cloud Native Applications
Architecting Cloud Native ApplicationsArchitecting Cloud Native Applications
Architecting Cloud Native Applications
WSO2
 

Recently uploaded (20)

Exploring Multimodal Embeddings with Milvus
Exploring Multimodal Embeddings with MilvusExploring Multimodal Embeddings with Milvus
Exploring Multimodal Embeddings with Milvus
 
Apidays New York 2024 - APIs in 2030: The Risk of Technological Sleepwalk by ...
Apidays New York 2024 - APIs in 2030: The Risk of Technological Sleepwalk by ...Apidays New York 2024 - APIs in 2030: The Risk of Technological Sleepwalk by ...
Apidays New York 2024 - APIs in 2030: The Risk of Technological Sleepwalk by ...
 
Repurposing LNG terminals for Hydrogen Ammonia: Feasibility and Cost Saving
Repurposing LNG terminals for Hydrogen Ammonia: Feasibility and Cost SavingRepurposing LNG terminals for Hydrogen Ammonia: Feasibility and Cost Saving
Repurposing LNG terminals for Hydrogen Ammonia: Feasibility and Cost Saving
 
Strategies for Landing an Oracle DBA Job as a Fresher
Strategies for Landing an Oracle DBA Job as a FresherStrategies for Landing an Oracle DBA Job as a Fresher
Strategies for Landing an Oracle DBA Job as a Fresher
 
MINDCTI Revenue Release Quarter One 2024
MINDCTI Revenue Release Quarter One 2024MINDCTI Revenue Release Quarter One 2024
MINDCTI Revenue Release Quarter One 2024
 
Understanding the FAA Part 107 License ..
Understanding the FAA Part 107 License ..Understanding the FAA Part 107 License ..
Understanding the FAA Part 107 License ..
 
Apidays New York 2024 - The Good, the Bad and the Governed by David O'Neill, ...
Apidays New York 2024 - The Good, the Bad and the Governed by David O'Neill, ...Apidays New York 2024 - The Good, the Bad and the Governed by David O'Neill, ...
Apidays New York 2024 - The Good, the Bad and the Governed by David O'Neill, ...
 
Vector Search -An Introduction in Oracle Database 23ai.pptx
Vector Search -An Introduction in Oracle Database 23ai.pptxVector Search -An Introduction in Oracle Database 23ai.pptx
Vector Search -An Introduction in Oracle Database 23ai.pptx
 
FWD Group - Insurer Innovation Award 2024
FWD Group - Insurer Innovation Award 2024FWD Group - Insurer Innovation Award 2024
FWD Group - Insurer Innovation Award 2024
 
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemke
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemkeProductAnonymous-April2024-WinProductDiscovery-MelissaKlemke
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemke
 
Corporate and higher education May webinar.pptx
Corporate and higher education May webinar.pptxCorporate and higher education May webinar.pptx
Corporate and higher education May webinar.pptx
 
Introduction to Multilingual Retrieval Augmented Generation (RAG)
Introduction to Multilingual Retrieval Augmented Generation (RAG)Introduction to Multilingual Retrieval Augmented Generation (RAG)
Introduction to Multilingual Retrieval Augmented Generation (RAG)
 
MS Copilot expands with MS Graph connectors
MS Copilot expands with MS Graph connectorsMS Copilot expands with MS Graph connectors
MS Copilot expands with MS Graph connectors
 
Why Teams call analytics are critical to your entire business
Why Teams call analytics are critical to your entire businessWhy Teams call analytics are critical to your entire business
Why Teams call analytics are critical to your entire business
 
CNIC Information System with Pakdata Cf In Pakistan
CNIC Information System with Pakdata Cf In PakistanCNIC Information System with Pakdata Cf In Pakistan
CNIC Information System with Pakdata Cf In Pakistan
 
Architecting Cloud Native Applications
Architecting Cloud Native ApplicationsArchitecting Cloud Native Applications
Architecting Cloud Native Applications
 
Apidays New York 2024 - The value of a flexible API Management solution for O...
Apidays New York 2024 - The value of a flexible API Management solution for O...Apidays New York 2024 - The value of a flexible API Management solution for O...
Apidays New York 2024 - The value of a flexible API Management solution for O...
 
"I see eyes in my soup": How Delivery Hero implemented the safety system for ...
"I see eyes in my soup": How Delivery Hero implemented the safety system for ..."I see eyes in my soup": How Delivery Hero implemented the safety system for ...
"I see eyes in my soup": How Delivery Hero implemented the safety system for ...
 
Rising Above_ Dubai Floods and the Fortitude of Dubai International Airport.pdf
Rising Above_ Dubai Floods and the Fortitude of Dubai International Airport.pdfRising Above_ Dubai Floods and the Fortitude of Dubai International Airport.pdf
Rising Above_ Dubai Floods and the Fortitude of Dubai International Airport.pdf
 
WSO2's API Vision: Unifying Control, Empowering Developers
WSO2's API Vision: Unifying Control, Empowering DevelopersWSO2's API Vision: Unifying Control, Empowering Developers
WSO2's API Vision: Unifying Control, Empowering Developers
 

Molbiol 2011-07-chromosomes-cell-cycle

Editor's Notes

  1. XV. 1 XV) cell cycle ( Alberts Ch. 17) A) Phases of the cell cycle (M, G1, S, G2) 1) M = Mitosis 2) G1, S, and G2 make up interphase B) review of mitosis 1) M phase includes mitosis and cytokinesis 2) several events occur during mitosis 3) M phase can be divided into 6 stages a) prophase b) prometaphase c) metaphase d) anaphase e) telophase f) cytokinesis C) Cell cycle time varies D) Regulation of the Cell Cycle by cell growth and extracellular signals 1)G1 restriction point a) occurs late in G1 b) controls progression from G1 to S c) first defined in Saccharomyces cerevisiae - START d) passage through START in yeast is highly regulated e) most animal cells have a G1 restriction point analogous to START XV. 2 2) Some cell cycles are controlled via a G2 restriction point a) Schizosaccharomyces pombe b) oocytes E) Checkpoints 1) G2 checkpoint a) senses unreplicated DNA b) senses damaged DNA 2) G1 checkpoint a) also recognizes damaged DNA b) mediated by p53 3) M phase checkpoint F) Identification of MPF 1) experiments with xenopus oocytes 2) experiments in mammalian cells 3) experiments in yeast 4) studies in sea urchin embryos G) purification and characterization of MPF from xenopus 1) MPF contains two components a) a cyclin dependent kinase (CDK) called Cdc2 b) a mitotic cyclin - cyclin B 2) MPF activity cycles H) MPF (CyclinB/cdc2) controls G2-M transition XV. 3 1) Cyclin B synthesis begins in S phase 2) Cyclin B accumulates and forms complexes with Cdc2 throughout S and G2 3) Cdc2 is phosphorylated on three regulatory positions 4) Thr 15 and Tyr 15 get dephosphorylated by cdc25 5) active cdc2 phosphorylates a variety of target proteins a) nuclear lamins b) Histone H1 c) MAPs d) other targets 6) Cdc2 activity also triggers the degradation of cyclin B 7) cdc2 is then inactivated 8) cells exit mitosis, undergo cytokinesis, return to interphase I) Cyclin B and cdc2 are members of large families of proteins 1) yeast contain multiple cyclins 2) higher eukayrotes have multiple cyclins and cdc2 related kinases ( CDKs) J) The activities of the Cdks are regulated by multiple mechanisms 1) association of the Cdks with their cyclin partners 2) stimulatory phosphorylation sites 3) inhibitory phosphorylation sites 4) binding of inhibitory proteins ( CKIs - Cdk inhibitors) K) Growth factors and the D type cyclins 1) cells require growth factors to pass from G1 to S 2) Cyclin D synthesis is induced in response to growth factors 3) Cyclin D concentration falls if growth factors are removed XV. 4 4) Cyclin D/Cdk4 drives cells through the restriction point 5) Cyclin D overexpression is associated with cancer 6) CKIs such as p16 can inhibit Cdk4/Cyclin D complexes L) Rb is a key substrate of cyclin D1 1) Rb is a product of the gene responsible for retinoblastoma 2) Rb is also associated with other cancers 3) Rb is a tumor suppresser gene 4) Rb phosphorylation is regulated throughout the cell cycle 5) Rb becomes phosphorylated by Cdk4/Cyclin D complexes as cells pass through G1 restriction point 6) unphosphorylated Rb binds members of the E2F family 7) binding Rb inhibits E2F’s ability to activate transcription 8) phosphorylation of Rb results in its dissociation from E2F 9) E2F then activates target genes M) p53 acts to stimulate expression of p21 1) p21 inhibits the cell cycle progression in two ways a) it is a CKI that inhibits several Cdk/cyclin complexes b) It may also directly inhibit DNA replication in S phase 2) expression of the p21 gene is induced by p53 N) TGF  inhibits cell proliferation in many epithelial cells 1) TGFB arrests cells at G1 2) TGFB induces the CKI p15 and p27 3) p15 and p27 bind Cdk4/Cyclin D 4) In the absence of Cdk4 activity, Rb phosphorylation is blocked and the cell cycle is arrested at G1 Figures from Alberts: 17-14, 17-19, Panel 18-1