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Human cells growing in culture divide about once every __. In the body, the time taken to pass through a single cell cycle is usually longer but the events that take place are the same in all cases. These events are coordinated and controlled to ensure that __, and that __, when it occurs, results in the __.
- 24 hours
- the chromosomes are replicated at the appropriate time
- cell division
- orderly partitioning of the replicated chromosomes into the daughter cells.
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Dividing cells pass through repeated cycles of __—the period when __ and __ occur—and __, a less dramatic period when few dynamic changes can be detected with the LM Interphase took on a new importance as the period when __
- mitosis
- nuclear and cell division
- interphase
- genome replication must take place.
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The cell cycle has four stages. What are they?
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G1
longest phase in which the cell grows, metabolizes, and, within a multicellular organism, performs its specialized function
During G1, the cell has its standard complement of chromosomes, 46 for a diploid human cell
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S phase
period when the chromosomal DNA molecules are replicated. At the start of it, the replication origins are activated and bidirectional DNA synthesis progresses along the linear molecules until replication is complete; can take up to 6 to 8 hours to complete
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G2
Because the cell is already committed to division, G2 lasts about 3-4 hours; during this phase, the cell is tetraploid, as each chromosome has been replicated and contains two DNA molecules.
At the end of this phase, the chromosomes begin to condense to form the metaphase structures. This leads to the M phase, when nuclear and cell division take place
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M phase
nuclear and cell division take place
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What are hte two types of nuclear division?
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mitosis
Mitosis gives rise to two daughter nuclei, each containing the same chromosome complement as the parent, and is the standard type of division for somatic cells
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Meiosis
Meiosis is the specialized type of cell division that gives rise to the male and female reproductive cells
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DNA replication must be coordinated with the rest of the cell cycle
DNA replication must be coordinated with the other phases of the cell cycle so that what happens?
the genome is completely replicated but replicated only once before mitosis occurs.
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Coordination of the cell cycle involves a variety of regulatory proteins, called __
Some are active at the __ and so are thought to __. Others __, while the cell is preparing itself for mitosis
- cyclins
- beginning of S phase
- switch on DNA replication
prevent a second round of DNA replication from occurring during the G2 phase
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Cyclins are thought to influence DNA replication by doing what?
The initiation of DNA rep at an origin requires __, which is converted to __, when the replication forks move away from the origin
- regulating events at the replication origin
- construction of an pre-replication complex (pre-RC)
- post-replication complexes (post-RCs)
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A post-RC is unable to __, which means that segments of the genome that have been replicated cannot what?
- initiate replication
- be accidentally recopied before mitosis has occurred.
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The key protein involved in construction of a pre-RC is __
Inactivation of this gene showed that cells were unable to __. When Cdc6p is overexpressed, what happens?
Cdc6p
synthesize pre-RCs
large amounts of the protein are made--> genome undergoes multiple rounds of replication in the absence of mitosis
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Cdc6p is synthesized during __ and recruits the __ into the __. This helicase is probably responsible for __
- G1 phase
- MCM helicase protein
- pre-RC
- breaking the base pairs withi the origin, allowing DNA synthesis to begin
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A second important group of pre-RC protiens are the __, which become bound to the chromosomal DNA toward the end of__ and remain in place until the start of__, after which they are gradually removed from the DNA as it is replicated
- replication licensing factors (RLFs)
- M phase
- S phase
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The removal of RLFs may be the key event that __ and so __.
- converts a pre-RC into a post-RC
- prevents reinitiation of replication at an origin that has already directed a round of replication
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Control can also be exerted during __
Though the G1 to S phase control point is a major control, there are more controls
Initiation of replication does not occur at the same time at all replication origins, nor is “__” an entirely random process
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Some parts of the genome are replicated early in S phase and some later, the pattern of replication being consistent from one round of the cell cycle to the next
The general pattern is that __ and __ are replicated early in __, and __and __ of each chromosome later on
Early firing origins are therefore __ and reflect the pattern of __ occurring in a particular cell.
The migration rate of __also shows variability
- actively transcribed genes and the centromere
- S phase
- telomeres
- nontranscribed regions
- tissue-specific
- gene expression
- individual replication forks
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The firing time is determined not simply by the __ because transfer of a DNA segment from its normal position to another site in the same or a different chromosome can result in a __. The positional effect may be linked with the way that the __
- sequence of the origin
- change in the firing pattern of origins contained in that segment
- DNA is packaged in different parts of a chromosome
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The position of the origin in the nucleus may also be important as __that become active at similar periods within S phase appear to be __
- origins
- clustered together
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DNA replication can be brought to halt during S phase if __.
This response is linked with the __ whose products are __. A set of __respond to signals from proteins that detect the __
- DNA damage occurs
- activation of genes
- involved in DNA repair
- S-phase cyclins
- presence of damage in the template DNA at a replication fork.
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The signals from these __can elicit different types of cellular response
1) The replication process can be __
If the damage is not excessive, then DNA repair processes are __
damage-sensing proteins
arrested by repressing the firing of origins of replication that are usually activated at later stages in S phase or by slowing the progression of existing replication forks.
activated and replication is subsequently able to recommence
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Alternately, apoptosis may occur to prevent __
DNA damage from giving rise to tumor or other cancerous growth
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In mammals, a central player in induction of cell cycle arrest and apoptosis is the protein called __. This is classified as a __ because when this protein is defective, cells with damaged genomes can avoid the __and possibly proliferate into a __
- p53
- tumor-suppressor protein
- S-phase checkpoints
- cancer
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P53 is a __that does what, and it also __
sequence-specific DNA-binding protein
activates a number of genes thought to be directly responsible for apoptosis
represses expression of other genes that must be switched off to facilitate these processes
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Mitosis ensures the correct partitioning of chromosomes
Following a successful S phase--> __--> 2 daughter cells with a complete set of chromosomes
The chromosomes were replicated during __, so at the start of mitosis each one contains two daughter DNA molecules attached to one another at the __. The chromosomes are still in their __, comprising regions of __ and __
- mitosis
- S phase
- centromere
- interphase conformations
- euchromatin and heterochromatin
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Mitosis has five stages. What are they?
- prophase
- prometaphase
- metaphase
- anaphase
- telophase
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prophase
chromosomes condense and become visible under LM; nuclear membrane breaks down and centrosomes of cell move to either side of the nuclear region
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prometaphase
chromosomes are now fully condensed and begin to attach to the microtubules radiating out from the centrosomes
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metaphase
chromosomes line up in the middle of the nuclear region
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Anaphase
each pair of replicated chromosomes separates; one member of each pair is drawn toward one of the centrosomes. During the later part of anaphase, the cell begins to constrict around its middle
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Telophase
completes a round of mitosis; the chromosome pairs are fully separated and new nuclear membranes are being formed around each set; the middle of the cell contains to constrict until division is complete
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How is the appropriate partitioning of chromosomes assured?
The answer lies in the structure of the metaphase chromosome and the positioning of the kinetochores on the surface of the conjoined centromeres. Two kinetochores form, one on each centromere. The two kinetochores are therefore on opposite sides of the chromosome pair
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The kinetochores are the __. The centrosomes are themselves located __, the microtubular arrangmenet that now occupies the region of the cell previously taken up by the nucleus
- attachment points for the microtubules that radiate out from the centrosomes
- on the opposite sides of the mitotic spindle
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During prometaphse, the microtubules of the spindle begin to __, migrating along the __until they locate one or the other of the kinetochores
The first microtubule to locate a kinetochore will do what?
The other kinetochore is now more likely to __
- attach to the chromosomes
- chromatids
- orient that kinetochore toward the centrosome to which the microtubule is attached
- be caught by a microtubule from the other centrosome
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Eventually, up to __ will attach to either kinetochore.
The two sets of microtubules begin to pull in opposite directions, the tension that is set up dong what? If both kinetochores have been captured by microtubules from the same centrosome, then __
- 40 microtubules
- confirming that the correct attachments have been made
- this tension is not generated and mitosis cannot continue
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At the start of anaphase, the __ that hold the daughter chromosomes together are degraded by __, and the microtubules begin to draw the freed daughters toward the __
The natural outcome is that one of the daughter chromosomes of each pair __, and the other __. The result is that a complete set of chromosomes is assembled at each of the poles of the mitotic spindle
- cohesion proteins
- protease enzymes
- centrosomes
- moves toward one centrosome
- toward the other centrosome
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During telophase, __ within a new nucleus. Division of the cell—__—occurs across the plane of the mitotic spindle, ensuring that each daughter cell forms around __. Each daughter cell therefore inherits a __ and hence a complete copy of the parent cell’s genome
- each set becomes enclosed
- cytokinesis
- one of the divided nuclei
- complete set of chromosomes
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