This slideshow contains various stages of cell cycle regulation, cell cycle checkpoints and their proteins involved in regulation. Cell cycle checkpoints transition phases.
Basic Cell cycle regulation suitable for undergraduate students.
This presentation has been started from the basics to enable easy understanding. It covers all the details of cell cycle regulation in yeast as well as higher eukaryotes.
This presentation on "Cell Cycle regulation" takes you to the cell cycle describing the stages and checkpoints involved providing some of the evidences of cell cycle regulation. Then we will move to cyclins and cyclin dependent kinases and the mechanism they follow.
This journey in regulation of cell cycle will take a halt after a general discussion of positive and negative cell cycle regulators.
Thankyou.
Cell cycle regulation presentation by me and my colleagues. Not the Best work but still it will give a general idea about DNA damage checkpoints, roles of Cdk-Cyclin complexes, Rb proteins, ATM&ATR kinases, p51, etc.
Reference : Nature reviews & The Cell a molecular approach. (cooper)
Basic Cell cycle regulation suitable for undergraduate students.
This presentation has been started from the basics to enable easy understanding. It covers all the details of cell cycle regulation in yeast as well as higher eukaryotes.
This presentation on "Cell Cycle regulation" takes you to the cell cycle describing the stages and checkpoints involved providing some of the evidences of cell cycle regulation. Then we will move to cyclins and cyclin dependent kinases and the mechanism they follow.
This journey in regulation of cell cycle will take a halt after a general discussion of positive and negative cell cycle regulators.
Thankyou.
Cell cycle regulation presentation by me and my colleagues. Not the Best work but still it will give a general idea about DNA damage checkpoints, roles of Cdk-Cyclin complexes, Rb proteins, ATM&ATR kinases, p51, etc.
Reference : Nature reviews & The Cell a molecular approach. (cooper)
INTRODUCTION
Definition
history
DIFFERENT PHASE
G0 PHASE
INTERPHASE
M PHASE
CHECKPOINT
HOW DOES IT WORK
Inhibitors
Mechanism of action
Function
CONCLUSION
references
Cell cycle refers to the set of events through which a cell grows, replicates its genome, and ultimately divides into two daughter cells through the process of mitosis.
https://www.creative-bioarray.com/cell-cycle-assays.htm
This presentation on "Cell Cycle regulation" takes you to the cell cycle describing the stages and checkpoints involved providing some of the evidences of cell cycle regulation. Then we will move to cyclins and cyclin dependent kinases and the mechanism they follow.
This journey in regulation of cell cycle will take a halt after a general discussion of positive and negative cell cycle regulators.
Thankyou.
The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to duplication of its DNA (DNA replication) and division of cytoplasm and organelles to produce two daughter cells.
By using flow cytometry, staining dyes are needed. Creative Bioarray can choose different dyes to perform the assays, including propidium iodide (PI), BrdU, 7-amino actinomycin-D (7-AAD), Hoechst 33342 and 33258, and 4’6’-diamidino-2-phenylindole (DAPI), based on the customer’s applications or requirements.
https://www.creative-bioarray.com/cell-cycle-assays.htm
in this presentation you will aware about regulation of cell cycle and the proteins involved in cancer study. How these protein regulated by cell cycle.
INTRODUCTION
Definition
history
DIFFERENT PHASE
G0 PHASE
INTERPHASE
M PHASE
CHECKPOINT
HOW DOES IT WORK
Inhibitors
Mechanism of action
Function
CONCLUSION
references
Cell cycle refers to the set of events through which a cell grows, replicates its genome, and ultimately divides into two daughter cells through the process of mitosis.
https://www.creative-bioarray.com/cell-cycle-assays.htm
This presentation on "Cell Cycle regulation" takes you to the cell cycle describing the stages and checkpoints involved providing some of the evidences of cell cycle regulation. Then we will move to cyclins and cyclin dependent kinases and the mechanism they follow.
This journey in regulation of cell cycle will take a halt after a general discussion of positive and negative cell cycle regulators.
Thankyou.
The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to duplication of its DNA (DNA replication) and division of cytoplasm and organelles to produce two daughter cells.
By using flow cytometry, staining dyes are needed. Creative Bioarray can choose different dyes to perform the assays, including propidium iodide (PI), BrdU, 7-amino actinomycin-D (7-AAD), Hoechst 33342 and 33258, and 4’6’-diamidino-2-phenylindole (DAPI), based on the customer’s applications or requirements.
https://www.creative-bioarray.com/cell-cycle-assays.htm
in this presentation you will aware about regulation of cell cycle and the proteins involved in cancer study. How these protein regulated by cell cycle.
By using flow cytometry, staining dyes are needed. Creative Bioarray can choose different dyes to perform the assays, including propidium iodide (PI), BrdU, 7-amino actinomycin-D (7-AAD), Hoechst 33342 and 33258, and 4’6’-diamidino-2-phenylindole (DAPI), based on the customer’s applications or requirements.
https://www.creative-bioarray.com/cell-cycle-assays.htm
Please answer all of #5 After the completion of S phase, F.2F functi.pdfsiennatimbok52331
Please answer all of #5 After the completion of S phase, F.2F function is no longer needed. pRb
must be dephosphorylated so that it can once again bind to E2F. Name the type of enzyme
responsible for removing phosphate groups from proteins. Knowing what you know about the
cell cycle, explain why the RB gene would be considered a tumor suppressor gene. Below are
listed four different mechanisms of regulating of cyclin/CDK activity. For each mechanism
explain how that mechanism regulates cyclin/CDK activity. Phosphorylation by WeeI
Dephosphorylation by Cdc 25 Binding by a cyclin dependent kinase inhibitor Degradation of
cyclins by the proteasome
Solution
5. A. Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission
yeast Schizosaccharomyces pombe (S. pombe). It has a molecular mass of 96 kDa and it is a key
regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis,
through inhibiting Cdk1. It has homologues in many other organisms, including mammals.
Wee1 inhibits Cdk1 by phosphorylating it on two different sites, Tyr15 and Thr14. Cdk1 is
crucial for the cyclin-dependent passage of the various cell cycle checkpoints. At least three
checkpoints exist for which the inhibition of Cdk1 by Wee1 is important:
B. Cdc25 is a dual-specificity phosphatase first isolated from the yeast Schizosaccharomyces
pombe as a cell cycle defective mutant. As with other cell cycle proteins such as Cdc2 and Cdc4,
the \"cdc\" in its name refers to \"cell division cycle\". Dual-specificity phosphatases are
considered a sub-class of protein tyrosine phosphatases. By removing inhibitory phosphate
residues from target Cyclin-Dependent Kinases (Cdks), Cdc25 proteins control entry into and
progression through various phases of the cell cycle, including mitosis and S (\"Synthesis\")
phase.
Cdc25 activates cyclin dependent kinases by removing phosphate from residues in the Cdk
active site. Also, the phosphorylation of M-Cdk (a complex of Cdk1 and cyclin B) activates
Cdc25. Together with Wee1, M-Cdk activation is switch-like. The switch-like behavior forces
entry into mitosis to be quick and irreversible. Cdk activity can be reactivated after
dephosphorylation by Cdc25. The Cdc25 enzymes Cdc25A-C are known to control the
transitions from G1 to S phase and G2 to M phase.
C. A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK
complex to block kinase activity, usually during G1 or in response to signals from the
environment or from damaged DNA. In animal cells, there are two major CKI families: the
INK4 family and the CIP/KIP family. The INK4 family proteins are strictly inhibitory and bind
CDK monomers. Crystal structures of CDK6-INK4 complexes show that INK4 binding twists
the CDK to distort cyclin binding and kinase activity. The CIP/KIP family proteins bind both the
cyclin and the CDK of a complex and can be inhibitory or activating. CIP/KIP family proteins
activate c.
WHAT IS CELL?
WHAT IS CELL DIVISION OR CELL CYCLE?
WHY DO CELL DIVIDE?
HISTORY
CELL CYCLE
INTERPHASE
M-PHASE
MOLECULAR EVENT DURING CELL CYCLE AND CELL REGULATION
TYPES OF CELL DIVISION
IMPORTANCE OF CELL DIVISION
ABNORMALTIES OF CELL CYCLE
REFRENCES
CELL CYCLE
CELL CYCLE CHECK POINT
PHASES IN CELL CYCLE CHECK POINT
ROLE OF CYLINE AND CDKS
MUTURATIONAL PROMOTING FACTOR
FUNCTION OF MPR
CONCLUSION
REFRENCE
The phenomenon of signal transduction, also known as cell signaling, pertains to the intricate mechanisms that facilitate the transfer of biological information between cells. The effective coordination of diverse specialized cell types in various tissues and organs is a prerequisite for the proper functioning of complex multicellular organisms, necessitating intercellular communication. This communication must be continuous and dynamic to maintain coordination. Additionally, cell signaling pathways play a crucial role in the mechanisms of action of numerous drugs, including both local and general anesthetics. Consequently, a fundamental understanding of cell signaling mechanisms is imperative for comprehending various pathophysiologic and pharmacologic mechanisms.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
1. The cell concept is the axis around which the
whole of the modern science of life revolves.
- Paul Ehrlich
2. Cell Cycle Regulation
Speaker:
Himakara Datta Mandalapu
M.Sc.(Ag.) previous year
Department of Genetics and Plant breeding
CoA, IGKV, Raipur.
GP 591 (0+1)
Master’s Seminar
7. Cell cycle regulation in Yeasts
(S.cerevisiae)
• Regulation occurs at a point in late G1 phase.
• Called as START point.
• Controls progression from G1 to S phase
• The passage through START is influenced by external signals such as
nutrient availability, mating factors, cell size etc.
• Analogous to restriction point in animal cells.
8. Regulation by START point
• If all the conditions are favorable – Proceeds to S phase.
• Low nutrient availability – enters a resting state till the optimum
availability of nutrients occur.
• Mating factors present – cell cycle arrested at START, and allows
haploid yeast cells to fuse to become diploid.
• Cell size of daughter cell not adequate – arrested at G1 till the
daughter cells become uniform in size.
9. • In animals cells, if appropriate growth factors are not present the
cells enter a quiescent stage called G₀ phase.
• The cells have arrested development in aforementioned phase but
are still metabolically active.
10. • Even though most of the cell division control takes place in G₁ phase,
some cell cycles are controlled in G₂ phase.
• Control takes place at G₂ to M phase
• Examples:
The cell cycle of fission yeast Schizosaccharomyces pombe.
• Oocytes of vertebrates remain arrested in G₂ for long periods of time
until their progression into M phase is triggered by hormonal
stimulation.
12. • The current concepts of cell‐cycle regulation focus on the idea of a
biochemical clock whose progression is regulated by a set of fail‐safe
monitors called checkpoints.
• Checkpoints are signaling pathways that detect cellular defects, stop
cell‐cycle progression, or initiate specific repair pathways.
13. • The coordination between the different phases of the cell cycle is
dependent on a series of cell cycle checkpoints.
• They prevent the entry of cell cycle into the next phase until the
preceding phase events have been completed.
15. • Size checkpoints at the molecular level is based on regulation of the
proteins involved in G1 and G2/M progression.
• Control of the G1 cell size checkpoint has been studied most
extensively in budding yeast, where the cyclin Cln3, which activates
Start, regulates cell size
• Control of the G2/M cell size checkpoint has been studied most
extensively in fission yeast, where Cdc25 and Wee1 respond to cell
size and nutritional status in their control of the Cdc2-cyclinB complex
17. Cyclin dependent kinases (Cdks)
• The central machines that drive cell cycle progression are the cyclin-
dependent kinases (CDKs).
• These are serine/threonine protein kinases that phosphorylate key
substrates to promote DNA synthesis and mitotic progression.
• The catalytic subunits are in molar excess, but lack activity until bound
by their cognate cyclin subunits.
• Cyclin subunits are tightly regulated at both the levels of synthesis and
ubiquitin-dependent proteolysis.
• All CDKs exist in similar amounts throughout the entire cell cycle.
18. • Cyclin-binding allows inactive CDKs to adopt an active
configuration akin to monomeric and active kinases.
• Layered on top of this regulation, CDK activity can also be
negatively regulated by the binding of small inhibitory
proteins, the CKIs, or by inhibitory tyrosine
phosphorylation which blocks phosphate transfer to
substrates.
19. • A Cdks is an enzyme that adds negatively charged
phosphate groups to other molecules in a process
called phosphorylation.
• Through phosphorylation, Cdks signal the cell that it is
ready to pass into the next stage of the cell cycle.
22. Cyclins
• Cyclins are named such because they undergo a constant cycle of
synthesis and degradation during cell division.
• When cyclins are synthesized, they act as an activating protein and
bind to Cdks forming a cyclin-Cdk complex.
• This complex then acts as a signal to the cell to pass to the next cell
cycle phase.
• Eventually, the cyclin degrades, deactivating the Cdk, thus signaling
exit from a particular phase.
23. • Common classes of cyclins include G1-phase cyclins, G1/S-phase
cyclins, S-phase cyclins, and M-phase cyclins.
• G1/S cyclins – essential for the control of the cell cycle at the G1/S
transition,
• Cyclin A / CDK2 – active in S phase.
• Cyclin D / CDK4, Cyclin D / CDK6, and Cyclin E / CDK2 – regulates
transition from G1 to S phase.
• G2/M cyclins – essential for the control of the cell cycle at the
G2/M transition (mitosis). Cyclin B / CDK1 – regulates progression
from G2 to M phase.
24.
25.
26.
27. Cell cycle stage Cyclins CDKs Comments
G1 Cyclin D CDK4&6
Can react to outside signals such
as growth factors or mitogens.
G1/S Cyclins E & A CDK2
Regulate centrosome duplication;
important for reaching START
S Cyclins E & A CDK2
Targets are helicases and
polymerases
M Cyclins A & B CDK1
Regulate G2/M checkpoint. The
cyclins are synthesized during S
but not active until synthesis is
complete. Phosphorylate lots of
downstream targets.
28. p53 – The Guardian of the genome
• p53, also known as TP53 or tumor protein is
a gene that codes for a protein that regulates the
cell cycle and hence functions as a tumor
suppression.
• Described as "the guardian of the genome",
referring to its role in conserving stability by
preventing genome mutation
• Activated p53 is stabilized through protection
from its E3 ubiquitin ligase Mdm2.
• p53 can direct the alternative cell fates of
apoptosis or senescence
29. • Trans activates the expression of a large number of genes, including
the cyclin-dependent kinase inhibitor (CKI) p21.
• Through this mechanism, G1 CDKs are inhibited, and DNA damage is
repaired prior to DNA replication.
• p53 can also repress the expression of genes, and is required for
prolonged G2 arrest in the face of persistent DNA damage.
• Defective p53 could allow abnormal cells to proliferate, resulting in
cancer.
30. Wee 1
• Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein
kinases in the fission yeast Schizosaccharomyces pombe (S. pombe).
• Wee1 is a key regulator of cell cycle progression. It influences cell size
by inhibiting the entry into mitosis, through inhibiting Cdk1.
• Wee1 acts as a dosage-dependent inhibitor of mitosis.
• Thus, the amount of Wee1 protein correlates with the size of the
cells
31. Anaphase promoting complex or
cyclosome (APC/C).
• E3 ubiquitin ligase that marks target cell cycle proteins for
degradation by the 26S proteasome.
• E3s mediate the transfer of one or several ubiquitin monomers
on a protein substrate in a two-step reaction involving at least
three partners.
• First, an ubiquitin-activating enzyme (E1) activates and transfers
ubiquitin to an ubiquitin-conjugating enzyme (E2).
• Next, E3 mediates the transfer of ubiquitin from E2 to a lysine
residue of the target protein.
• Activated by the phosphorylation by Cdk1/cyclin B complex.
32. Cell division cycle protein 20 (Cdc20)
• Activator protein that regulates the ubiquitin ligase activity and
substrate specificity of the anaphase promoting
complex/cyclosome (APC/C).
• Required for sister chromatid separation and disassembly of the
mitotic spindle. Target of the spindle checkpoint pathway through
participation in the mitotic checkpoint complex (MCC) and the
MAD2-CDC20 sub complex.
•
33. G1-S transition
• The primary G1/S cell cycle checkpoint controls the
commitment of eukaryotic cells to transition through the G1
phase to enter into the DNA synthesis S phase.
• Two cell cycle kinase complexes, CDK4/6-Cyclin D and CDK2-
Cyclin E, work in concert to relieve inhibition of a dynamic
transcription complex that contains the retinoblastoma protein
(Rb) and E2F.
34. Rb-E2F regulation
• In G1-phase uncommitted cells, hypo-
phosphorylated Rb binds to the E2F-DP1
transcription factors forming an inhibitory
complex
• Commitment to enter S-phase occurs through
sequential phosphorylation of Rb by Cyclin D-
CDK4/6 and Cyclin E-CDK2, permitting
transcription of genes required for DNA
replication.
36. G2/M transition
• Brought about by the Maturation Promoting Factor (MPF)
• MPF is made up of two subunits: Cdk1(protein kinase) and Cyclin
B(catalytic activity).
• Phosphorylation of Cdk1 at Thr161, Thr14, Tyr15 by Wee1
• Phosphorylation at Thr14, Tyr15 inhibits the Cdk1 activity.
• Dephosphorylation of Thr14, Tyr15 by a protein phosphatase Cdc25.
• Thus, the activated cdk1 phosphorylates a variety of proteins that
initiate the events of M phase.
37. Entry into Mitosis
• Regulated by Cdk1/Cyclin B complex along with two other kinases i.e.
Polo-like kinase and Aurora Kinase (A&B).
• Cdk1, Polo-like kinase and Aurora Kinase (A&B) as Mitotic Protein
Kinases (MPK).
• They are activated in a positively controlled feedback loop at the
onset of M phase.
• These interactions bring about multiple nuclear and cytoplasmic
changes during mitosis by phosphorylation of different proteins.
39. MPK interaction during Mitosis
MPKs Phosphorylating Protein Result
Cdk1 + Aurora kinase B Condensins
Chromatin condensationAurora B + Polo-like Kinase Cohesins
Aurora B kinase Histone H3 serine-10
Cdk1/Cyclin Lamins
Nuclear envelop breakdownCdk1 Proteins of inner nuclear
membrane & nuclear pore complex
Cdk1 and Polo like Kinases Golgi matrix proteins Breakdown of Golgi apparatus into
vesicles
Cdk1, Aurora A & Polo-like Kinases Microtubule associated proteins Centrosome maturation, separation
& spindle assembly
40. DNA damage checkpoints
• DNA damage checkpoints ensure that damaged DNA is not passed
on to the daughter cells.
• Function in G1, S, G2, phases of the cell cycle.
• Checkpoint at G2 phase – prevents the initiation of mitosis if the
DNA has not been completely replicated.
• Checkpoint at G1 phase – allows repair of damaged DNA before
entering S phase.
• S phase Checkpoint – continuous monitoring of the integrity of DNA
to ensure any damage of DNA to be repaired before replication.
41. • DNA damage checkpoints can be separated into those controlled by
the tumor suppressor and transcription factor p53, and those
ultimately under the control of the checkpoint kinase Chk1, Chk2
• Two protein kinases ATR and ATM are activated in response to DNA
damage.
• ATR acts on single strand breaks or unreplicated DNA.
• ATM acts on double strand breaks.
• Chk1,2 act by phosphorylating and inhibition of Cdc25.
42.
43. Spindle Assembly Checkpoints
• Also called as the ‘wait anaphase’ checkpoint, or the mitotic
checkpoint.
• Monitors the alignment of chromosomes on the metaphase spindle.
• Presence of even a single unaligned chromosome is enough to
prevent the activation APC/C.