Life starts as a single cell To grow develop and repair tissue damage We rely on cell division A human adult contain an estimated a 100 trillion cells Most Eukaryotes follow a process Of growth and division called a cell cycle

The cell cycle or cell-division cycle is

An orderly sequence of events that occurs in a cell Lead to cell division Duplication of its DNA (DNA replication) To produce two daughter cells It is a genetically controlled process In human being cell cycle goes for 24 hours In yeast cells it takes 90 minutes In E.Coli it takes 20 minutes

Cell's way of replicating itself gradually in an organized manner

to prepare cell for division create copies of organelles double the size of the cell check DNA for errors

Involves processes important for the continued existenceof a cell

Integrate the detection and repair of genetic damage Prevention of uncontrolled cell division Molecular events that control the cell cycle

are planned and directional Each process occurs in a sequential manner It is impossible to reverse the cycle

Example-Cancer results as a consequence of disruption of the normal regulation of the cell cycle

An extended G1 phase

Phase of cell differentiation Cell is neither dividing nor preparing to divide Reproductively resting (Resting phase) but functional Where the cell has left the cycle Sometimes also referred to as Post mitotic phase Cell cycle starts with this phase

Example -Hepatocytes (liver cells) do not divide except for injury to the liver

Quiescence of a cell can be reversible or irreversible

Reversible quiescence

Found in plant cells Where differentiated cells can show dedifferentiation Specialized structures are reversed to more simplified And the cells enter cell cycle

Some cells enter the G0 phase temporarily

Are considered post-mitoticExample- Few Liver Kidney and Stomach cells

Many cells do not enter G0

And continue to divide all through an organism's life Example - Epithelial cells

Irreversible quiescence In multicellular eukaryotes Non-proliferative (non-dividing) cells Usually enter the quiescent G0 state from G1 Can stay quiescent for long time (Indefinite period )

Nerve cells Osteoclasts Heart muscle cells ( Go cells)

Are permanently differentiated Never exhibit dedifferentiation Become post-mitotic (stop dividing) when they reach maturity But carry on major functions all through life of organism

Multinucleated muscle cells

That do not undergo cytokinesis Are also often considered to be in the G0 stage

Go PHASE OF CELL CYCLE

Cell cycle includes the following eventsGrowth Phase (Inter phase)

M Phase ( Mitosis)

(Karyokinesis and Cytokinesis)

A sequence of changes

Occur in newly created cell and its nucleus Before it becomes capable of division again Prior to cell division Cell needs to obtain nutrients Preparations for cell division are made

(Preparatory phase)

No apparent activity related to cell division (Resting / Non dividing phase)

Cell is engaged in Growth and high metabolic activities

Takes 95% of cell cycle

Inter phase can be further divided into three distinct phases :

G1 Phase (Gap1 phase)

S Phase (Synthesis Phase)

G2 Phase (Gap2 Phase)

The growth phase First phase inside inter phase After M phase till the start of DNA synthesis Cell grows and functions normally Volume of cytoplasm increases Cell grows to about double its original size Cytoplasmic components and organelles Including centrioles in animal cells replicate mRNA synthesized High amount of protein synthesis( histones ) occurs If cell is not to divide again it will enter Go

Most non proliferating vertebrate cells enter the G0 phase

In this phase the cell duplicates its DNA Chromosomes have been replicated Each chromosome has two sister chromatids Amount of DNA in the cell has doubled Though the ploidy ( no of sets of chromosomes) of the

cell remains the same RNA transcription and and protein synthesis are very low Except histone production which largely occurs during this

phase

Period of protein synthesis And rapid cell growth Prepares cell for mitosis Mitochondria divide Cell continues to grow until mitosis begins In plants chloroplasts also divide during G2 Ends with the onset of prophase stage of mitosis

A part of the cell cycle Single cell divides into two identical daughter cells

(cell division)

Replicated chromosomes get separated Into two new nuclei (Karyokinesis) Followed by Cytokinesis when Cytoplasm, Organelles and Cell membrane Divide into two new cells Holding about equal distribution of cellular components

Mitosis and cytokinesis together describe the mitotic M Phase of an animal cell cycle

The chief purpose of mitosis is

Growth and replacement of damaged cells If not corrected instantly errors made during mitosis Consequently result in changes in the DNA Potentially lead to genetic disorders

Karyokinesis is the division of nucleus thattakes place in four stages :

1. PROPHASE 2. METAPHASE 3. ANAPHASE 4. TELOPHASE

Chromosomes condense Into X-shaped structures Become visible Pairing as two sister chromatids Containing identical genetic information Held together at the centromere Cytoskeleton disassembles

(Network of protein filaments and microtubules in cytoplasmthat controls cell shape maintains intracellular organization )

Spindle begins to form Centrioles migrate to opposite poles Establishing a bridge of microtubules Called the Spindle Apparatus Nuclear envelope breaks down

Towards the end of prophase

Chromosomes attach To microtubules from each pole By the proteins in their centromeres (kinetochores ) Moving the chromosomes Towards the equator of the cell

During this all the chromosomes are aligned At the equator of the cell called Metaphase

Plate

Begins with the degradation of proteins That hold sister chromatids together Freeing the individual chromosomes Free chromosomes are pulled By their kinetochores To opposite poles

A cleavage furrow appears in the centre of the cell This groove is made from a contracting belt Of actin filaments inside the cell circumference Chromosomes cluster at the opposite poles Began decondensing Nuclear envelope reforms around them Spindle apparatus disassembles Microtubules break down into tubulin monomers To shape the cytoskeleton of the daughter cells

Completes cell division in animal cells

By extending the cleavage To completely separate Newly formed daughter cells

In plants Cell wall cannot be constricted by actin fibers Vesicles form Increasing the membrane partition Called the Cell Plate Cytokinesis completes with Division of the contents of cytoplasm Between the two identical daughter cells

One of several positions in eukaryotic cell cycle On which progression of a cell To subsequent stage in cycle can be arrested Until conditions are favorable

CP’s are control modes

To make certain that proper cell division occurs Since it is necessary to facilitate that Daughter cells are precise replica of the parent cell Errors in replication or distribution of chromosomes Cause mutations that might pass further to every new cell

(formed from an abnormal cell)

The three internal checkpoints that evaluate the state of the genetic information

The G1 / Restriction or Start checkpoint / Major Checkpoint

The G2 / M checkpoint

The Metaphase / Spindle checkpoint

Checks whether

Cell has enough raw materials To fully replicate its DNA Nucleotide bases DNA synthase Chromatin etc Cell size , Energy reserves , Protein reserves Damage to DNA and other external causes are assessed Unhealthy or malnourished cell will get caught Will not be allowed To carry on to S phase of interphase Or will go back into G0 (Inactive) phase And await further signals

If a cell completes the requirements for the G1 checkpoint It will enter S phase And begin DNA replication If DNA has been correctly replicated Cyclin dependent kinases (CDK’s) Signal commencement of mitosis

Cyclins are cell-signaling molecules that regulate the cell cycle

G1 CHECKPOINT is also identified as

The Restriction Point (in mammalian cells )And

The Start Point (in yeast)

The G2 checkpoint ensures

All the chromosomes have been replicated That replicated DNA is not damaged before cell

enters mitosis That cell has enough cytoplasm and phospholipids for two

daughter cells If it is the proper time to replicate Sometimes many cells ought to replicate simultaneously

( Example a growing embryo should have a proportionate cell distribution )

If checkpoint mechanism

• Detect problems with DNA• Cell cycle gets halted• Cell attempts to either • Complete DNA replication• Or repair damaged DNA

• If DNA has been correctly replicated Cyclin dependent kinases(CDKs)

• Signal the start of mitosis

Occurs near the

End of metaphase stage of mitosis Ensures that kinetochores Of each pair of sister chromatids Are firmly attached To spindle microtubules As the separation of sister chromatids During anaphase is an irreversible step Cycle will not proceed until All chromosomes are firmly attached To at least two spindle fibers From opposite poles of cell

The checkpoints control cell cycle

Reliability of DNA is assessed at G1 checkpoint

Proper chromosome duplication is assessed atG2 checkpoint

Attachment of each kinetochore to a spindle fiber is assessed at M checkpoint

Once all checkpoints in Inter phase are cleared

Mitosis occurs from Inter phase to cytokinesis Entire process of cell division takes An average 10-20 hours in a typical plant or animal cell Depending on nature and use of cell In humans, skin cells Go through mitosis very frequently Due to wear and tear

Cells like Neurons and muscle cells rarely divide

Accuracy of mitosis as well as Uniformity of checkpoints Ensure that most cells in eukaryotic organisms Can produce identical copies of themselves This process allows for growth and repair

To prolong overall Physiology and Life

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