RNA.
? RNA is polymer of ribonucleotides.
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? Linked together by 3'-5' phosphodiester bond.? Function of RNA-
? Protein synthesis.
? Genetic material.
? Ribozymes.
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?TYPES OF RNA.
? Messenger RNA
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mRNA? m RNA
? Transfer RNA
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t RNA
? T RNA
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? Ribosomal RNAr RNA
? R RNA
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GENE REGULATION.? Gene regulation refers to the mechanism that act to induce or
repress the expression of a gene.
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Level of Gene control.? Gene on DNA
? |
? - -Transcriptional control
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?? Primary transcript
?
? ( RNA processing control)
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m RNA( RNA transport control )
| -- Translation control.
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Protein
TYPES OF RNA.
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m ? RNA- messenger.
Translation.
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r-RNA- ribosomalProtein synthesis.
t- RNA- transfer
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translation
Sn-RNA-- small nuclear
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m RNA processing poly a additionSno-RNA---small nucleolar
r- RNA processing/ maturation,
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methylation.
Regulatory RNA---siRNA and miRNA
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Regulation of transcription and translation.Regulatory RNAs.
? Small nuclear RNA
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Sn RNA? Sn RNA
? micro
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mi RNA
? RNA
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? Small interferringSi RNA
? RNA
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REGULATORY RNA.? Inhibition of gene expression.
siRNA
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? Inhibition of gene expression.
mi RNA
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? Tumour suppression and oncogenes.? Primary transcript RNA.
Nascent RNA ? Needs to be processed like--capping, RNA splicing.
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PHASE OF CELL CYCLE? G1---- (Gap-1)--Phase.
? S-------Synthetic phase.
? G2- --- Gap-2 Phase.
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? M-------Mitotic phase.? G1, S, and G2-----Interphase--cell prepare to divide.
? M phase---Both DNA and cytoplaslm divide to produce two
daughter cells.
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PHASE OF CELL CYCLE.INTERPHASE.
INTERPHASE- G1 PHASE.
? 1st growth stage after cell division.
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? Cells matures by making more cytoplasm and organelles.? Cells carries on its normal metabolic activity.
? S-STAGE-
? synthesis stage.
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? DNA is copied or replicated.INTERPHASE --G2 - stage
? 2nd growth stage.
? Occurs after DNA has copied.
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? All cell structure needed for division are made.(eg-centriole).? Both organelles and proteins are synthesized.
? DNA replicates, centriole if present replicate.
? cell prepares for division.
MITOSIS.
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MITOSIS.? Division of nucleus also called karyokinesis.
? Has four stages.
? Four mitotic stages are--
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? Prophase.? Metaphase.
? Anaphase.
? Telophase.
?
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Early prophase.? Chromatin in nucleus condenses to form visible chromosome.
? Mitotic spindle forms.
? Late Prophase? nuclear membrane and nucleolus
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are broken down.
? Chromosome condenses and clearly visible.
? Spindle fibre called kinetochore attach to the centromere of
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each chromosome.
? Spindle finishes forming between the poles of the cell.
?
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METAPHASE.? Chromosomes, attached to the kinetochores fibre, move to
the centre of the cell.
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? Chromosomes now lined up at the equator.
ANAPHASE --
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? occurs rapidly.? Chromatids are pulled apart to opposite poles
by kinetochores fibres.
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?TELOPHASE.
? Sister chromatids at opposite poles.
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? Spindle disasembles.? Nuclear envelope forms.
? Nucleolus reappears.
? Cytokinesis occurs.
? Chromosome reappear as chromatin.
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CYTOKINESIS.? Means division of cytoplasm.
? Division of cell into two identical half called daughter cells .
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? Daughter cells of mitosis have same number of chromosomesthat of parent cell.
? Must grow in size to become mature cells.( G1 of Interphase)
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METAPHASE.ANAPHASE.
TELOPHASE.
PHASE OF CELL CYCLE AND REGULATION.
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Cyclin D ,CDK-4G2-
G1
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cdk1
S ?cyclin
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E,cdk2ROLE OF CDK-1 COMLEX IN G2 CHECK POINT
REGULATION.
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? CYCLIN B--CDK-P ---INACTIVE? <- Active protein kinase <-
DNA strand break.
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? |? CYCLIN ?B CDK-1 ---ACTIVE
? |
? Phosphorylation of several protein.
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? |? Bipolar spinle formation -----MITOSIS.
Cyclin and cdk molecule.
FIVE PHAGES OF THE CELL CYCLE.
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? G1--Primary growth phase.? S---synthesis, DNA replicated.
? G2--secondary growth phase.
? Collectively these 3 stages are called interphase.
? M--mitosis.
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? C--cytokinesis.CELL CYCLE REGULATION.
? Why cell cycle cycle regulation-------
? cell division is expensive process.
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? Maintain integrity of genome.? Proper cellular homeostasis.
? Prevent onset of mutation.
KEY REGULATOR.
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Cdk/cyclin dependent protein,catalytic protein.? Cyclin, regulatory protein.
Apart from these , two other important regulator....
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? (Rb protein and p53 protein.)-Tumours suppressor protein.
Oncogenes also disrupt cell cycle.
? P53 is a tumor suppressor gene ?
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? p53 gene produces a protein with amolecule mass of 53kDa.This protein suppresses the tumour
formation. it arrest the cell cycle at G2/M check point.
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Mutation in p53 gene are found in 50% of all cancer.
? It distrupts cell cycle both at G1/S and G2/M check point by
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coding for a CDK inhibitors called p21 which binds to severalcyclin CDK comlexes influencing the cell cycle.
BCL2 GENE.
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? BCL2 gene associated with beta ? cell lymphoma appears toinduce cyclin D gene. Excess cyclin D expression could result in
unrestained cell division leading to cancer.
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? CDK INHIBITORS----------
? CDK are inhibited by CDK inhibitors
which are produced in response to signal like DNA damage.
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These inhibitor lead to arrest of cell cycle.
CYCLINS.
? They named because they undergo a cycle of synthesis of
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degradation in each cycle.
? It is a regulatory protein of cell cycle and shows continuous
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rise and fall during the various stages of cell cycle.? Synthesis of cyclins proteins begins during G1 phase and they
increases their concentration till Metaphases but in anaphase
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they are degraded by the actvated by the actIvity of APC.
FOUR CLASSES OF CYCLINS.
? G1 CYCLINS---
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? Help to promote passes through " start" .? G1/S CYCLINS----
? Bind to Cdks at the end of G1 and commit cell to
DNA replication.
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? S-CYCLINS----
? Bind Cdks durindg S phase cand are required for
initiator of DNA replication.
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? M CYCLINS --Promote the event of mitosis.
Cyclin.
Cyclin is the important key regulator of cell cycle.
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? Cyclin...........
Also regulate the activity of cdk.(cyclin dependent kinase.)
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? Regulator of both cell cycle and cdk.CYCLIN DEPENDENT KINASE.
? Progression of cell cycle is controlled by a conserved
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set of protein called --KINASE
? KINASE.
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? Regulate the progression of cell cycle in association
with another group of protein called as--
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CDK? Cyclins.
? Concentration of cyclins fluctuates throughout the
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cell cycle
CYCLINS
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? Cyclins.DIFFERENT TYPES OF Cdk.
? G2 to M phase.
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Cdk1 ? G2 to M? G1 to S.
Cdk2 ? G1 to S phase.
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? G1 to S.
? Gap 1 to Synthetic phase.
cdk4
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Cdk 20--Metaphase to Anaphase....
THREE MAIN TRANSITION CHECK POINTS IN
CELL CYCLE.
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G1 TO S.
G2 TO M.
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METAPHASETO ANAPHASE.
G1 CHECK POINT.
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Checks conditions are favouringfor cell division.
Checks for genomic DNA damage
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at G1,adequate energy reserves,
DNA damage.
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Synthesis of G1 cyclins mustreach specific level to cross the
start point.
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Rb protein.(Retinoblastoma protein).? Classic tumour suoppressor.
? Its product called Rb protein prevents the cell to migrate from
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G1 to S Phase.? Master regulator of biological pathway like---
? Cell Growth, cell cycle checkpoints, differentiation,
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replication, genomic stability and apoptosis.P53 protein.
(GUARDIAN OF GENOME.)
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? Tumour suppressor gene.P53 PROTEIN.
? P53.
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? Preventing tumour developement
P53
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? p53? Inhibit over expression of cell.
P53
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? Regulate the cell cycle.