Like cohesin, condensin is an elongated complex of several proteins that binds and encircles DNA. In contrast to cohesin, which binds two sister chromatids together, condensin is thought to bind a single chromatid at multiple spots, twisting the chromatin into a variety of coils and loops Figure 3. During mitosis, chromosomes become attached to the structure known as the mitotic spindle.
In the late s, Theodor Boveri created the earliest detailed drawings of the spindle based on his observations of cell division in early Ascaris embryos Figure 4; Satzinger, Boveri's drawings, which are amazingly accurate, show chromosomes attached to a bipolar network of fibers. Boveri observed that the spindle fibers radiate from structures at each pole that we now recognize as centrosomes, and he also noted that each centrosome contains two small, rodlike bodies, which are now known as centrioles.
Boveri observed that the centrioles duplicate before the chromosomes become visible and that the two pairs of centrioles move to separate poles before the spindle assembles.
We now know that centrioles duplicate during S phase, although many details of this duplication process are still under investigation. It is now well-established that spindles are bipolar arrays of microtubules composed of tubulin Figure 5 and that the centrosomes nucleate the growth of the spindle microtubules. During mitosis, many of the spindle fibers attach to chromosomes at their kinetochores Figure 6 , which are specialized structures in the most constricted regions of the chromosomes.
The length of these kinetochore-attached microtubules then decreases during mitosis, pulling sister chromatids to opposite poles of the spindle.
Other spindle fibers do not attach to chromosomes, but instead form a scaffold that provides mechanical force to separate the daughter nuclei at the end of mitosis. From his many detailed drawings of mitosen, Walther Flemming correctly deduced, but could not prove, the sequence of chromosome movements during mitosis Figure 7.
Flemming divided mitosis into two broad parts: a progressive phase, during which the chromosomes condensed and aligned at the center of the spindle, and a regressive phase, during which the sister chromatids separated.
Our modern understanding of mitosis has benefited from advances in light microscopy that have allowed investigators to follow the process of mitosis in living cells. Such live cell imaging not only confirms Flemming's observations, but it also reveals an extremely dynamic process that can only be partially appreciated in still images.
Mitosis begins with prophase, during which chromosomes recruit condensin and begin to undergo a condensation process that will continue until metaphase.
In most species , cohesin is largely removed from the arms of the sister chromatids during prophase, allowing the individual sister chromatids to be resolved. Cohesin is retained, however, at the most constricted part of the chromosome, the centromere Figure 9. During prophase, the spindle also begins to form as the two pairs of centrioles move to opposite poles and microtubules begin to polymerize from the duplicated centrosomes.
Prometaphase begins with the abrupt fragmentation of the nuclear envelope into many small vesicles that will eventually be divided between the future daughter cells. The breakdown of the nuclear membrane is an essential step for spindle assembly.
Because the centrosomes are located outside the nucleus in animal cells, the microtubules of the developing spindle do not have access to the chromosomes until the nuclear membrane breaks apart. Prometaphase is an extremely dynamic part of the cell cycle. Microtubules rapidly assemble and disassemble as they grow out of the centrosomes, seeking out attachment sites at chromosome kinetochores, which are complex platelike structures that assemble during prometaphase on one face of each sister chromatid at its centromere.
As prometaphase ensues, chromosomes are pulled and tugged in opposite directions by microtubules growing out from both poles of the spindle, until the pole-directed forces are finally balanced. Sister chromatids do not break apart during this tug-of-war because they are firmly attached to each other by the cohesin remaining at their centromeres. At the end of prometaphase, chromosomes have a bi-orientation, meaning that the kinetochores on sister chromatids are connected by microtubules to opposite poles of the spindle.
Next, chromosomes assume their most compacted state during metaphase, when the centromeres of all the cell's chromosomes line up at the equator of the spindle. Metaphase is particularly useful in cytogenetics , because chromosomes can be most easily visualized at this stage. Furthermore, cells can be experimentally arrested at metaphase with mitotic poisons such as colchicine. Video microscopy shows that chromosomes temporarily stop moving during metaphase. A complex checkpoint mechanism determines whether the spindle is properly assembled, and for the most part, only cells with correctly assembled spindles enter anaphase.
Figure 10 Figure Detail. Figure 9. The progression of cells from metaphase into anaphase is marked by the abrupt separation of sister chromatids. A major reason for chromatid separation is the precipitous degradation of the cohesin molecules joining the sister chromatids by the protease separase Figure Two separate classes of movements occur during anaphase. During the first part of anaphase, the kinetochore microtubules shorten, and the chromosomes move toward the spindle poles. During the second part of anaphase, the spindle poles separate as the non-kinetochore microtubules move past each other.
These latter movements are currently thought to be catalyzed by motor proteins that connect microtubules with opposite polarity and then "walk" toward the end of the microtubules.
Mitosis ends with telophase, or the stage at which the chromosomes reach the poles. The nuclear membrane then reforms, and the chromosomes begin to decondense into their interphase conformations. Telophase is followed by cytokinesis, or the division of the cytoplasm into two daughter cells. The daughter cells that result from this process have identical genetic compositions.
Cheeseman, I. Molecular architecture of the kinetochore-microtubule interface. Nature Reviews Molecular Cell Biology 9 , 33—46 doi Cremer, T. Chromosome territories, nuclear architecture and gene regulation in mammalian cells.
Nature Reviews Genetics 2 , — doi Hagstrom, K. Condensin and cohesin: More than chromosome compactor and glue. Nature Reviews Genetics 4 , — doi Hirano, T. At the heart of the chromosome: SMC proteins in action. Nature Reviews Molecular Cell Biology 7 , — doi Mitchison, T. Throughout interphase, nuclear DNA remains in a semi-condensed chromatin configuration.
In the S phase, DNA replication results in the formation of identical pairs of DNA molecules, sister chromatids, that are firmly attached to the centromeric region. The centrosome is duplicated during the S phase. The two centrosomes will give rise to the mitotic spindle, the apparatus that orchestrates the movement of chromosomes during mitosis. At the center of each animal cell, the centrosomes of animal cells are associated with a pair of rod-like objects, the centrioles, which are at right angles to each other.
Centrioles help organize cell division. Centrioles are not present in the centrosomes of other eukaryotic species, such as plants and most fungi. In the G 2 phase, the cell replenishes its energy stores and synthesizes proteins necessary for chromosome manipulation.
Some cell organelles are duplicated, and the cytoskeleton is dismantled to provide resources for the mitotic phase. There may be additional cell growth during G 2. The final preparations for the mitotic phase must be completed before the cell is able to enter the first stage of mitosis.
During the multistep mitotic phase, the cell nucleus divides, and the cell components split into two identical daughter cells. The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and move into two new, identical daughter cells.
The first portion of the mitotic phase is called karyokinesis or nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into the two daughter cells. Karyokinesis, also known as mitosis, is divided into a series of phases prophase, prometaphase, metaphase, anaphase, and telophase that result in the division of the cell nucleus.
Stages of the Cell Cycle : Karyokinesis or mitosis is divided into five stages: prophase, prometaphase, metaphase, anaphase, and telophase. The images at the bottom were taken by fluorescence microscopy hence, the black background of cells artificially stained by fluorescent dyes: blue fluorescence indicates DNA chromosomes and green fluorescence indicates microtubules spindle apparatus.
The membranous organelles such as the Golgi apparatus and endoplasmic reticulum fragment and disperse toward the periphery of the cell. The nucleolus disappears and the centrosomes begin to move to opposite poles of the cell. Microtubules that will eventually form the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly with the aid of condensin proteins and become visible under a light microscope.
The remnants of the nuclear envelope fragment. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and discrete. Each sister chromatid develops a protein structure called a kinetochore in the centromeric region. The proteins of the kinetochore attract and bind mitotic spindle microtubules.
Kinetochore and Mitotic Spindle : During prometaphase, mitotic spindle microtubules from opposite poles attach to each sister chromatid at the kinetochore. In anaphase, the connection between the sister chromatids breaks down and the microtubules pull the chromosomes toward opposite poles. The sister chromatids are still tightly attached to each other by cohesin proteins.
At this time, the chromosomes are maximally condensed. Or they can cause health problems in a child. A woman age 35 years or older is at higher risk of having a baby with a chromosomal abnormality.
This is because errors in meiosis may be more likely to happen as a result of the aging process. Women are born with all of their eggs already in their ovaries.
The eggs begin to mature during puberty. If a woman is 35 years old, the eggs in the ovaries are also 35 years old. Men make new sperm ongoing. But newer studies suggest that rare abnormalities do occur.
Mitosis my-TOH-sis is the dividing of all other cells in the body. Mitosis causes the number of chromosomes to double to 92, and then split in half back to
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