The Cell Cycle and Introduction to Lamins - Week 18

Question 1

why do cells divide

Answer 1

cells divide for the following reasons:
*Efficiency
– Small cells have a higher surface area
* Repair
– Repair damaged cells
– Replace old cells
* Growth and development
– Survival
– Fertility

Question 2

how does cell division occur in prokaryotes

Answer 2

cell division in prokaryotes occurs through Binary fission.

Question 3

what happens in binary fission

Answer 3

– Binary fission
* DNA replicates - strands attach to the
membrane
* Cell elongates – DNA separates
* Cell wall and cell membrane grow from
the centre of the cell

Question 4

how does cell division occur in eukaryotes

Answer 4

2 types of division occur in eukaryotes:
- Meiosis – production of gametes
- Mitosis – occurs in all other dividing cells

Question 5

what is the meaning of the cell cycle

Answer 5

A sequence of events that take place in a cell leading to the duplication of DNA followed by cell division and formation of two daughter cells.

Question 6

what are the 2 main stages of the cell cycle and what happens in those stages

Answer 6

2 main stages of the cell cycle:
– Interphase – cell grows, replicates DNA
– Mitosis and cytokinesis – nucleus and nuclear
material divide and cytoplasm divides

Question 7

how long does a cell cycle last

Answer 7

The duration of each phase differs depending on the
cells but the cell cycle lasts about 18 hours. The G1 phase typically lasts 8-10 hours and the G2 phase typically lasts 4-6 hours.

Question 8

what happens if errors occur during the cell cycle

Answer 8

During the cell cycle, it is essential that the daughter cells are exact duplicates of the
parent cell. Errors in the duplication or distribution of chromosomes lead to mutations or damage in the DNA that can be passed on to daughter cells.

Question 9

what are checkpoints

Answer 9

checkpoints are points in a eukaryotic cell cycle at which the progression to the next stage can be halted for DNA repair or apoptosis to occur.

Question 10

what are the 3 main checkpoints in the cell cycle

Answer 10

The cell cycle has three main checkpoints:
* G1/S checkpoint – restriction point
* G2/M checkpoint
* M checkpoint (spindle checkpoint)

Question 11

what are 2 independent processes

Answer 11

DNA replication and organelle duplication are independent processes

Question 12

what is tightly regulated

Answer 12

Duplication and segregation of cellular components are tightly regulated

Question 13

how is coordination achieved in each phase of the cell cycle

Answer 13

Coordination is achieved by a family of tightly regulated protein kinases called cyclin-dependent kinases (CdKs).
Each phase is defined by the activation and inactivation of distinct members of this family.

Question 14

who won the noble prize in Medicine in 2001 and for what

Answer 14

• Leland H. Hartwell
• Tim Hunt
• Sir Paul M.Nurse

they won the Noble Prize in Medicine in 2001 for their discoveries of ‘ key regulators of the cell cycle’

Question 15

what is cyclin and why is it needed

Answer 15

Cyclins are regulatory proteins that associate with Cdks.
CdKs need to bind with a cyclin subunit to be active.

Question 16

how is CdKs activity controlled

Answer 16

The control of CdKs activity is the periodic presence and absence of cyclin subunits.

Question 17

what are cyclin levels through the cell cycle

Answer 17

Cyclin expression cycle

Question 18

what is the principles of control by David O Morgan cell cycle

Answer 18

Cyclin levels through the cell cycle

Question 19

what is the activity of CdKs through the cell cycle

Answer 19

expression and activities of cyclins and Cdks

Question 20

how are Cdks activated

Answer 20

CDKs require the presence of cyclins to become active. Cyclins are a family of proteins that have no enzymatic activity of their own but activate CDKs by binding to them.

Question 21

when are Cdks inactive

Answer 21

Deactivation requires both degradation of the cyclin molecule and de-phosphorylation by a CDK-associated phosphatase.
thus, without the cyclin, the Cdk is inactive and must wait for cyclin levels to rise again before it can be re- activated.

Question 22

what are the 4 major mechanisms of CdK regulation

Answer 22

The four major mechanisms of CDK regulation are:
- cyclin binding
- CAK phosphorylation,
- regulatory inhibitory phosphorylation
- binding of CDK inhibitory sub-units (CKIs).

Question 23

what are some features of the interphase - G1

Answer 23

• Intermediate phase
• The cell grows in size
• mRNA and proteins required for DNA synthesis
  (histones) are synthesised
• Organelles are duplicated
• Requires CdK 4 and 6
• Requires Cyclin D

Question 24

what is the restriction point and where does it occur

Answer 24

The restriction point,. also known as the “R” point or the “G1 checkpoint,” is a critical regulatory point in the cell cycle that determines whether a cell proceeds to divide or enters a resting state known as the G0 phase. The restriction point occurs during the interphase of the cell cycle

Question 25

what happens at the restriction point

Answer 25

At the restriction point, the cell undergoes a decision-making process where it evaluates its internal and external conditions, growth factors and the integrity of its DNA. If the cell receives positive signals indicating favorable conditions, it will pass the restriction point and enter the S phase to replicate its DNA and progress to cell division. However, if the conditions are unfavorable, the cell may delay or halt its progression through the cell cycle, entering a quiescent state called G0 phase or undergoing programmed cell death, known as apoptosis.

Question 26

what is pRb

Answer 26

The pRb protein functions as a negative regulator of the cell cycle, particularly at the G1/S transition, by inhibiting the activity of CdKs.
CdKs are enzymes that help regulate the progression of the cell cycle by phosphorylating target proteins. pRb acts by binding to CDKs, preventing their activation, and inhibiting the phosphorylation of target proteins that are necessary for cell cycle progression.

Question 27

what happens when pRb is active or inactive

Answer 27

One of the key functions of pRb is to control the activity of a protein called E2F, which is a transcription factor that regulates the expression of genes involved in cell cycle progression.
When pRb is in its active, unphosphorylated form, it binds to E2F and prevents its activity, thereby inhibiting the expression of genes that promote cell proliferation.
However, when pRb is phosphorylated by CDKs, its inhibitory activity is diminished, allowing E2F to become active and stimulate the transcription of genes required for cell cycle progression.

Question 28

when there is DNA damage in G1, what happens when DNA damage checkpoint kinase (ATM) activates ChK2 and ChK2 inhibits Cdc25a

Answer 28

• DNA damage checkpoint kinase (ATM) activates ChK2
• Checkpoint kinase (ChK2) inhibits Cdc25a (phosphatase)
• Cdc25 can no longer activate CdK2
• CdK2 can no longer phosphorylate/inactivate Rb protein

This results in:
* Cell cycle arrest and DNA repair
* Apoptosis

Question 29

when there is DNA damage in G1, what happens when DNA damage checkpoint kinase (ATM) activates ChK2 and ChK2 phosphorylates/activates p53

Answer 29

• DNA damage checkpoint kinase (ATM) activates ChK2
• Checkpoint kinase (ChK2) phosphorylates/ activates p53
• p53 activates the cyclin-dependent kinase inhibitor p21
• p21 inhibits CdK2
• CdK2 can no longer phosphorylate/inactivate Rb protein

This results in:
* Cell cycle arrest and DNA repair
* Apoptosis

Question 30

what are some sources of DNA damage

Answer 30

• Inherent in replication
• Ultraviolet light
• Other radiation - X, g, b
• Free radicals -reactive oxygen
• sugar! (glycation)
• Sun, food, stress, breathing,
  drinking, etc.

Question 31

what is p53

Answer 31

p53 is a transcription factor, which means it regulates gene expression by binding to specific DNA sequences and influencing the transcription of target genes. As a transcriptional activator, p53 can enhance the transcription of genes that promote cell cycle arrest, DNA repair, and apoptosis, among other cellular responses to DNA damage.
p53 also activates genes involved in repair and p53 is also responsible for growth arrest.

Question 32

what happens when p53 active p21

Answer 32

When p53 is activated in response to DNA damage or other cellular stresses, when p53 binds to the p21 gene, it leads to increased transcription and subsequent translation of p21 protein. Once produced, p21 acts as a cyclin-dependent kinase (CDK) inhibitor, which inhibits the activity of CDK-cyclin complexes that are involved in regulating the cell cycle progression.
By inhibiting CDKs, p21 helps to induce cell cycle arrest and p53 Interacts directly with the replication machinery to halt replication. This cell cycle arrest and pause in replication gives the cell time to repair its DNA and prevents the progression of potentially damaged DNA to daughter cells,

Question 33

what happens in the S phase

Answer 33

During the S phase of the cell cycle, DNA is replicated, resulting in the formation of two identical copies of each chromosome. This process is essential for cell division, as each daughter cell needs to have a complete set of genetic information.

In addition to DNA replication, the S phase also involves the detection and repair of DNA damage. This helps to maintain the integrity of the genetic material and prevent mutations occurring.

Question 34

what is the S phase characterized by

Answer 34

In human cells, the S phase is characterized by having 46 pairs of chromosomes, which is the typical number of chromosomes in a diploid cell. Each chromosome consists of two sister chromatids, which are the duplicated copies of the original chromosome resulting from DNA replication. These sister chromatids are held together by protein structures called centromeres.

Question 35

what regulates the progression the S phase

Answer 35

The progression of the S phase is tightly regulated by the activity of specific proteins, such as cyclin A and cyclin-dependent kinase 2 (CdK2).
The cyclin A-CdK2 complex helps to initiate and regulate DNA replication during the S phase, ensuring that DNA is replicated accurately and completely before the cell progresses to the next phase of the cell cycle.

Question 36

what happens at interphase - G2

Answer 36

• Cell growth in size and preparation
  for cell division
• Enzymes are synthesized for
  mitosis

Question 37

what is the G2/M checkpoint and what happens at the G2/M checkpoint

Answer 37

The G2/M checkpoint, also known as the pre-mitotic checkpoint, is a critical regulatory point in the cell cycle that occurs after the S phase and before mitosis (M phase).
At the G2/M checkpoint, the cell undergoes a series of checks to ensure that DNA replication has been completed without errors and that the DNA is undamaged.

Question 38

when there is DNA damage and ATR activates ChK1, what are the 3 pathways that inhibit CdK1 and what this result in

Answer 38

when there is DNA damage then the DNA damage checkpoint kinase (ATR) activates ChK1

• Checkpoint kinase (ChK1) inhibits Cdc25a
  (phosphatase)
• Cdc25 can no longer activate CdK1
• Checkpoint kinase (ChK1) activates Wee1
• Wee1 inhibits CdK1
• Checkpoint kinase (ChK1) phosphorylates/
  activates p53
• p53 activates the cyclin-dependent kinase
  inhibitor p21
• p21 inhibits CdK1

This Results in:
* Cell cycle arrest
* Apoptosis

Question 39

what happens during mitosis

Answer 39

During mitosis, the cell’s DNA, which has been duplicated during the S phase, undergoes separation and segregation to create two identical daughter cells with the same number of chromosomes.

Question 40

what regulates the progression of mitosis and what is the function of cyclin B-Cdk1 complex

Answer 40

The progression of mitosis is tightly regulated by various proteins and enzymes, including cyclin B and cyclin-dependent kinase 1 (CdK1), also known as mitosis-promoting factor (MPF). Cyclin B-CdK1 complex is responsible for driving the cell through the various stages of mitosis and ensuring that the events occur in a coordinated and timely manner.

Question 41

what happens at prophase in mitosis

Answer 41

– Chromosomes condense
– Nuclear envelope disappears
– Spindles move to different sides of cells
– Spindle fibres (kinetochore) attach to the centromeres of chromosomes

Question 42

what happens at metaphase in mitosis

Answer 42

Chromosomes line up in the center of the cell

Question 43

what happens at anaphase in mitosis

Answer 43

– Centromeres ‘snap’
– One copy of each chromosome is pulled to opposite poles by the spindle

Question 44

what happens at telophase in mitosis

Answer 44

– Chromosomes de-condense
– Nuclear envelope reappears

Question 45

what is spindle checkpoint

Answer 45

The spindle checkpoint is a regulatory mechanism that ensures proper chromosome segregation during cell division. It monitors the attachment of chromosomes to the spindle fibers and delays the progression of the cell cycle until all chromosomes are properly attached and aligned. Once all chromosomes are properly attached, the spindle checkpoint is satisfied, and the APC is activated, leading to the degradation of proteins that are necessary for sister chromatid cohesion. This allows the sister chromatids to separate and move towards opposite poles of the cell during anaphase.

Question 46

what is APC and why is it required

Answer 46

During anaphase, the activation of a protein complex called the anaphase-promoting complex or APC also occurs. The APC is an enzyme that plays a key role in regulating the progression of the cell cycle by targeting specific proteins for degradation. In particular, the APC targets proteins that are required for the cohesion between sister chromatids, allowing them to separate.

Question 47

what is MPF and why is it needed

Answer 47

MPF is a complex of proteins that regulates the progression of the cell cycle. When MPF is activated, it triggers the onset of mitosis by promoting various events, including the formation of the mitotic spindle. The active form of MPF phosphorylates target proteins that are needed for spindle formation and chromosome segregation.

Question 48

why is the attachment of microtubules to chromosomes essential

Answer 48

The attachment of microtubules to the chromosomes is essential for their proper alignment and segregation during mitosis. Incorrect attachment or detachment of microtubules can result in errors in chromosome segregation, leading to aneuploidy, which is an abnormal number of chromosomes in daughter cells.

Question 49

in short what are spindles made of and what is there function

Answer 49

spindles are dynamic structures composed of microtubules that play a crucial role in mitosis, including the initiation of mitotic events, proper alignment and segregation of chromosomes, and regulation of the metaphase/anaphase transition through checkpoint mechanisms.

Question 50

what are centrosomes and how are spindle fibers formed

Answer 50

Centrosomes are small structures located near the nucleus of a cell that serve as organizing centers for microtubules.

During mitosis, microtubules emanate from the centrosomes and attach to the kinetochores of the chromosomes at one end, forming spindle fibers that are responsible for pulling the chromatids apart during anaphase.

Question 51

what is Kinetochore and MAD2

Answer 51

The kinetochore is a protein complex that forms at the centromere of each chromatid during mitosis. It serves as the attachment site for spindle fibers and plays a crucial role in the proper alignment and segregation of chromosomes.

MAD2 (Mitotic Arrest-Deficient 2) is a protein that is a component of the kinetochore. It acts as a key regulator in the spindle checkpoint, which monitors the proper attachment of chromosomes to the spindle fibers.

Question 52

what happens when microtubules are properly attached and why a cyclin B required

Answer 52

During the transition from metaphase to anaphase in mitosis, when microtubules are properly attached to all chromosomes and tension is generated, MAD2 is no longer released from the kinetochores. This leads to the activation of an enzyme called the anaphase-promoting complex (APC), which targets the degradation of cyclin B.

Cyclin B is a protein that is required for the activation of MPF, which is a complex of proteins that drives cells into mitosis. The degradation of cyclin B by APC leads to the inactivation of MPF, triggering the onset of anaphase. This allows the sister chromatids to separate and segregate towards opposite poles of the cell, ensuring that each resulting daughter cell receives a complete set of chromosomes.

Question 53

why is the degradation of cyclin B and inactivation of MPF important

Answer 53

The degradation of cyclin B and subsequent inactivation of MPF is a critical step in the progression of the cell cycle, as it allows for proper chromosome segregation during anaphase and completion of mitosis. The spindle checkpoint, including the role of MAD2, helps to ensure that all chromosomes are properly attached to the spindle fibers before triggering the degradation of cyclin B and initiating chromosome segregation.

Question 54

what regulates the transition from metaphase to anaphase

Answer 54

the transition from metaphase to anaphase during mitosis is regulated by the attachment of microtubules to the kinetochores, which involves the release of MAD2 and prevents the destruction of cyclin B, ensuring proper chromosome segregation and progression of the cell cycle.

Question 55

how is the nuclear structure important in cell division

Answer 55

Nuclear structure plays a crucial role in supporting cell division, which is the process by which cells replicate and divide to form new cells.
As the nuclear structure provides the necessary support and organization for DNA replication, chromosome segregation, and other cellular processes during cell division, making it an essential component of the cell division process.

Question 56

what is the nuclear lamina and where is it located

Answer 56

The nuclear lamina is a network of intermediate filaments and associated proteins that is located inside the nucleus, specifically beneath the inner nuclear membrane of the nuclear envelope.

Question 57

what are the main functions of nuclear lamina

Answer 57

the nuclear lamina is a critical component of the nuclear structure, and it plays important roles in chromatin organization, nuclear pore complex anchoring, nuclear stability, and cell division, all of which are essential for proper nuclear function and cellular processes.

Question 58

what is the nuclear envelope

Answer 58

The nuclear envelope consists of two lipid bilayers, the inner nuclear membrane and the outer nuclear membrane, with a space called the perinuclear space between them. The nuclear lamina is associated with the inner nuclear membrane and forms a proteinaceous meshwork that underlies the membrane. Lamins, along with other associated proteins, help to anchor the nuclear lamina to the inner nuclear membrane, providing structural support to the nucleus.

Question 59

what is the Nuclear pore complex

Answer 59

The nuclear pore complex (NPC) is a large protein complex that spans the nuclear envelope and serves as a gatekeeper for the movement of molecules between the nucleus and the cytoplasm in eukaryotic cells. It is a highly dynamic structure and It plays a critical role in nuclear-cytoplasmic transport, gene expression, nuclear organization, signal transduction, and cell division.

Question 60

what disease is caused by mutations in lamins

Answer 60

Mutations in lamins, the intermediate filament proteins that form the nuclear lamina, have been associated with a number of diseases, including Progeria, which is a rare genetic disorder characterized by premature aging.
Progeria, also known as Hutchinson-Gilford Progeria Syndrome (HGPS), is a rare and severe genetic disorder that causes rapid and premature aging in children. Most cases of Progeria are caused by a spontaneous mutation in the LMNA gene.

Question 61

what is Progeroid laminopathies

Answer 61

Progeroid laminopathies are a group of rare genetic disorders that are caused by mutations in the LMNA gene, which codes for lamin A and lamin C, intermediate filament proteins that form the nuclear lamina. These mutations disrupt the normal structure and function of the nuclear lamina, leading to a wide range of cellular defects and ultimately resulting in premature aging and various clinical manifestations.

Question 62

what does the structural and mechanistic basis of Progeroid laminopathies involve

Answer 62

The structural and mechanistic basis of progeroid laminopathies involves several key aspects, including alterations in nuclear shape, disrupted gene expression, impaired DNA repair, and altered cellular signaling.