Bio Lecture 11 Objectives
Explain how the cell cycle control system controls movement through the cell cycle through a series of cell cycle checkpoints. •List the conditions necessary for cells to pass each checkpoint. •Describe why it is important for cells to meet these conditions. In other words, what is the logic for control at each checkpoint?)
- At specific points in the cell cycle, the cell is subjected to a checkpoint, in which the cell surveys the conditions within and surrounding the cell and makes a decision whether or not to continue progressing through the cell cycle. - Checkpoints ensure that cells only divide under the appropriate conditions and that each key process in the cell cycle occurs in the proper sequence Conditions G1 -> S - for unicellular organisms (such as yeast), there must be sufficient nutrients present. In contrast, for animal cells, growth factors must be present. - The second condition is that there must not be any DNA damage. - for unicellular organisms, cells should not begin to divide if there aren't enough nutrients to support doubling - In a multicellular organism, it is not in the organism's best interest to allow individual cells to make the decision whether or not to divide. Rather, it is in the multicellular organism's interest for the individual cells to obey signals that are regulated at the organismal level. - The decision is ultimately not left up to the cell! When cells go rogue and "decide" to divide on their own (for example, if they have mutations that inactivate the G1 checkpoint), this could be the beginning of tumor biogenesis. - It is not in cell's interest to replicate DNA that is damaged. If damaged DNA is replicated, DNA polymerases are not good at interpreting damaged template DNA sequence and they likely to introduce the incorrect nucleotide into a growing DNA strand when they encounter damage. This is one way that mutations arise. G2 -> M - DNA must be fully replicated. - any damaged DNA detected must be repaired. - in the M phase, one copy of the entire genome is distributed to each daughter cell. If the DNA has not been replicated, it is not possible to deliver one complete genome to each daughter cell. This checkpoint ensures that each daughter cell receives the complete complement of DNA. - similar to the G1 checkpoint, the cell does not want to pass on damaged DNA onto a daughter cell. Metaphase -> Anaphase - that every chromosome must be properly attached to the mitotic spindle. - Cells shouldn't begin pulling sister chromatids apart if they are not properly situated. If sister chromatids are not properly attached to kinetochore microtubules emanating from centrosomes at each pole of the mitotic spindle, the cell would not distribute one copy of every chromosome to each daughter cell. It is likely that daughter cells arising from such a situation would have too many or too few chromosomes.
Describe the mechanism of bacterial cell division.
- FtsZ is required for proper bacterial cell division to occur - Bacterial cells divide in a mechanism called binary fission. - First starts with a bacterial cell with a single circular chromosome. This DNA molecule is duplicated in the process of DNA replication. - At the end of replication, the two DNA molecules remain interlinked. The enzyme topoisomerase unlinks the two molecules by catalyzing the cleavage and rejoining of DNA molecules. - The two daughter DNA molecules are physically attached to the interior of the plasma membrane of the bacterial cell. - The cell begins to build new cell material and expands its cell membrane by inserting lipids between into the membrane these two DNA molecules. - As new lipids are inserted into the membrane and the cell wall is expanded, these two DNA molecules are pushed apart. - When the new cell wall and membrane are fully developed, the bacterial cell splits into two daughter cells, each of which have a single copy of the bacterial genome
Describe each stage of Interphase. •Explain what happens during each stage.
- Interphase is divided into three phases: G1, S, and G2. - G stands for Gap. There are two gaps: Gap 1 and Gap 2. - Most cellular components are synthesized continuously throughout all stages of interphase - It is the transition of G1 into the S phase that generally commits a cell into carrying out cell division G1 - the gap between M phase and S phase. - Most of the variation in generation time between different cells is based on differences in length of time spent in G1 - Before a cell begins DNA replication, it must ensure that it is biologically ready to take on such a process. G1 is the phase when this cellular monitoring takes place. S - stands for synthesis (nuclear DNA synthesis, in particular). - S phase the stage of the cell cycle in which nuclear DNA is replicated. - the phase of the cell cycle when DNA packaged into chromosomes is replicated G2 - the gap between S phase and M phase. - an intermediate phase, a time for the cell to ensure that it is ready to proceed in the cell cycle. - the cell's final chance to grow before it is split into two independent cells during mitosis
Outline the process of eukaryotic cell division.
- The cell divides, and one copy of each duplicated DNA molecule is distributed to each of the two daughter cells. - eukaryotic cells divide using the processes of mitosis. - Mitosis is common to all eukaryotes; during this process, a parent cell splits into two genetically identical daughter cells, each of which contains the same number of chromosomes as the parent cell.
Define and outline the process of apoptosis •Explain three reasons an organism might commit apoptosis. •Contrast apoptosis with necrosis. •Describe the ways apoptosis can be initiated. •Describe the major types of enzymes that are involved in apoptosis.
- the death of cells which occurs as a normal and controlled part of an organism's growth or development. stage one - the chromatin condenses and accumulates near the periphery of the nucleus and the volume of the cytoplasm decreases and the cell begins to shrink. stage two - the nucleus fragments. Cellular proteins are cleaved by a class of protease enzymes called caspases. DNA molecules are cleaved by Enzymes called DNases. The cell begins to form blebs (which are bubble-like cytoplasmic projections) that extend from the cell surface. stage three - the cell is dismantled into smaller apoptotic bodies that are bound by membranes (this prevents the contents from leaking into the extracellular space and harming neighboring cells and tissues). These apoptotic bodies are ingested by immune system cells called macrophages in the process of phagocytosis. - can be simulated by the absence of survival factors. Some cells require survival factors, which are essentially signaling molecules that inhibit cell death in the cells they interact with. - Cells secrete proteins called survival factors that prevent the apoptosis of neurons that have formed functional synapses (neuronal pruning) - can be stimulated by the presence of death signals - Cells infected by certain viruses are induced to undergo apoptosis by proteins called death signals from immune system cells (cytotoxic T cells) - Irreparable cellular damage (e.g. DNA, organelles) induces a cell to synthesize death signals to stimulate its own apoptosis - Apoptosis, or programmed cell death, is a form of cell death that is generally triggered by normal, healthy processes in the body. Necrosis is the premature death of cells and living tissue. Caused by factors external to the cell or tissue, such as infection, toxins, or trauma.
Explain how cells regulate passage through the cell cycle .•Describe and explain the roles and regulation of cyclin-dependent kinases (CDKs) and cyclins .•Explain the roles of centrosomes, cohesin, actin, myosin, condensing, securin, separase, and Maturation Promoting Factor (MPF), and Anaphase Promoting Complex (APC) in regulating progression through mitosis and the cell cycle.
CDKs - phosphorylate protein molecules. - Specifically, CDKs phosphorylate proteins to cause specific changes that bring about certain steps of the cell division cycle, depending on when the CDK is active. Cyclins - allosteric regulators of CDKs. - When bind to a CDK, it stabilizes an active conformation of the CDK. Centrosomes - functions as a microtubule-organizing center Cohesin - required to keep the sister chromatids together until their separation at anaphase - created by multi-protein subunit complexes called cohesins. Actin - provides mechanical support - determines cell shape - allows movement of the cell surface - enables cells to migrate, engulf particles, and divide. Myosin - can bind both actin and microtubules Condensing - The reorganization of the long thin chromatin strands into compact short chromosomes Securin - prevents premature sister-chromatid separation during mitosis Separase - dissolves the cohesion between sister chromatids, allowing the chromosomes to be partitioned to the two daughter cells. MPF - phosphorylates proteins that trigger mitotic events - phosphorylates and activates APC APC - triggers cyclin degradation and MPF inactivation
Describe the major processes and events occurring at each stage of mitosis and cytokinesis .• Explain the temporal relationship between mitosis and cytokinesis.
Mitosis - the separation of duplicated DNA molecules and nuclear division. - at the beginning of M phase, each chromosome contains two double-stranded DNA molecules. - during M phase, the sister chromatids are separated and delivered to daughter cells. Each chromatid is then considered to be a chromosome in its own right. - the separation of sister chromatids and the division of one nucleus into two - major goal of mitosis is to deliver one copy of each chromosome (or sister chromatid) into the nucleus of each daughter cell. Prophase - a cell is said to be in prophase when individual chromosomes are visible by light microscopy Prometaphase - the centrosomes complete their migration to opposite poles, or ends, of the nucleus. - the nuclear envelope becomes fragmented. - The inner and outer nuclear membrane break into small membrane-bound vesicles - The compartment that was the nucleus is no more in beginning in prometaphase. - Only after the sister chromatids have been successfully delivered to opposite poles of the dividing cell will the nuclear envelopes reform to encapsulate the DNA. - the chromosomes attach to the kinetochore microtubules of the forming mitotic spindles. Metaphase - the condensed chromosomes align at a plane that is equidistant between the two poles of the mitotic spindle - this plane is called the metaphase plate or the spindle equator. - the pulling, tugging of each sister chromatid toward the poles causes the alignment of chromosomes along the metaphase plate or spindle equator Anaphase - the cohesin protein that holds the sister chromatics together is proteolytically cleaved. - An enzyme called separase will snip or cleave cohesin, which had been functioning as a kind of glue or bonding agent holding the sister chromatids together. - Once cohesin is cleaved, The two sister chromatids of each chromosome will abruptly separate and be pulled toward opposite poles by the kinetochore microtubules. Telophase - the daughter chromosomes arrive at the opposite spindle poles, and they begin to uncoil, or decondense. - they then return to a state of chromatin present during interphase, where individual chromosomes are no longer visible as discrete entitites by light microscopy. - the nuclear envelope reforms to encapsulate the separated daughter chromosomes into individual nuclei. - these vesicles come back together and fuse to re-form the nuclear envelope. Cytokinesis - Divides the cytoplasm into two - cytokinesis typically begins before mitosis has completed, during telophase.
Describe the various components of the mitotic spindle .•Explain its role in mitosis .•Describe and explain the roles of kinetochores, centromeres, motor proteins, microtubule lengthening and shortening in proper segregation of sister chromatids to daughter cells.
Mitotic Spindle - The mitotic spindle includes two centrosomes (or microtubule organizing centers, or MTOCs) and the astral arrays of microtubules emanating from them. The centrosomes would be positioned at the heart of each of the astral arrays of microtubules - The major function of the mitotic spindle is to align the replicated chromosomes and then separate the sister chromatids for delivery to nuclei of the daughter cells. The spindle will provide the pulling force for sister chromatid separation and delivery. Kinetochores - link chromosomes to the spindle microtubules Centromeres -the portion of a chromosome that link two sister chromatids together and that form connections with kinetochore microtubules. - centromeres serve as the attachment sites for a few important proteins. Motor proteins - Proteins that use the energy of ATP hydrolysis to change their conformation, exert force, and cause attached structures to move - Depolymerize (shorten) kinetochore microtubules - Depolymerize (shorten) astral microtubules - Slide lengthening polar microtubules apart Microtubule lengthening and shortening in proper segregation of sister chromatids to daughter cells - Grow or shrink by adding or removing tubulin proteins at either end. - When a microtubule grows, new microtubule monomers (or subunits) are generally added to the so-called plus end. - When a microtubule shrinks, microtubule monomers (or subunits) are generally removed from the so-called minus end. - crucial for the delivery of sister chromatids to the nuclei of daughter cells