What is the difference between mitosis and interphase

Today, scientists know that Flemming had successfully distinguished chromosomes in the interphase portion of the cell cycle from chromosomes undergoing mitosis, or the portion of the cell cycle during which the nucleus divides Figure 1. With very few exceptions, mitosis occupies a much smaller fraction of the cell cycle than interphase.

The difference in DNA compaction between interphase and mitosis is dramatic. A precise estimate of the difference is not possible, but during interphase, chromatin may be hundreds or even thousands of times less condensed than it is during mitosis. For this reason, the enzyme complexes that copy DNA have the greatest access to chromosomal DNA during interphase, at which time the vast majority of gene transcription occurs.

In addition, chromosomal DNA is duplicated during a subportion of interphase known as the S, or synthesis, phase. As the two daughter DNA strands are produced from the chromosomal DNA during S phase , these daughter strands recruit additional histones and other proteins to form the structures known as sister chromatids Figure 2. The sister chromatids, in turn, become "glued" together by a protein complex named cohesin.

Cohesin is a member of the SMC, or structural maintenance of chromosomes, family of proteins. SMC proteins are DNA-binding proteins that affect chromosome architectures; indeed, cells that lack SMC proteins show a variety of defects in chromosome stability or chromosome behavior.

At the end of S phase, cells are able to sense whether their DNA has been successfully copied, using a complicated set of checkpoint controls that are still not fully understood. For the most part, only cells that have successfully copied their DNA will proceed into mitosis. The most obvious difference between interphase and mitosis involves the appearance of a cell 's chromosomes. During interphase, individual chromosomes are not visible, and the chromatin appears diffuse and unorganized.

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. During metaphase, all of the chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other. At this time, the chromosomes are maximally condensed.

During anaphase, the sister chromatids at the equatorial plane are split apart at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule was attached.

The cell becomes visibly elongated as the non-kinetochore microtubules slide against each other at the metaphase plate where they overlap. During telophase, all of the events that set up the duplicated chromosomes for mitosis during the first three phases are reversed.

The chromosomes reach the opposite poles and begin to decondense unravel. The mitotic spindles are broken down into monomers that will be used to assemble cytoskeleton components for each daughter cell.

Nuclear envelopes form around chromosomes. This page of movies illustrates different aspects of mitosis. Cytokinesis is the second part of the mitotic phase during which cell division is completed by the physical separation of the cytoplasmic components into two daughter cells.

Although the stages of mitosis are similar for most eukaryotes, the process of cytokinesis is quite different for eukaryotes that have cell walls, such as plant cells. In cells such as animal cells that lack cell walls, cytokinesis begins following the onset of anaphase. A contractile ring composed of actin filaments forms just inside the plasma membrane at the former metaphase plate. The actin filaments pull the equator of the cell inward, forming a fissure.

The furrow deepens as the actin ring contracts, and eventually the membrane and cell are cleaved in two Figure 6. In plant cells, a cleavage furrow is not possible because of the rigid cell walls surrounding the plasma membrane. A new cell wall must form between the daughter cells.

During interphase, the Golgi apparatus accumulates enzymes, structural proteins, and glucose molecules prior to breaking up into vesicles and dispersing throughout the dividing cell.

During telophase, these Golgi vesicles move on microtubules to collect at the metaphase plate. There, the vesicles fuse from the center toward the cell walls; this structure is called a cell plate. As more vesicles fuse, the cell plate enlarges until it merges with the cell wall at the periphery of the cell. Enzymes use the glucose that has accumulated between the membrane layers to build a new cell wall of cellulose. The Golgi membranes become the plasma membrane on either side of the new cell wall Figure 6.

Not all cells adhere to the classic cell-cycle pattern in which a newly formed daughter cell immediately enters interphase, closely followed by the mitotic phase. Cells in the G 0 phase are not actively preparing to divide. The cell is in a quiescent inactive stage, having exited the cell cycle. Some cells enter G 0 temporarily until an external signal triggers the onset of G 1. Other cells that never or rarely divide, such as mature cardiac muscle and nerve cells, remain in G 0 permanently Figure 6.

The length of the cell cycle is highly variable even within the cells of an individual organism. In humans, the frequency of cell turnover ranges from a few hours in early embryonic development to an average of two to five days for epithelial cells, or to an entire human lifetime spent in G 0 by specialized cells such as cortical neurons or cardiac muscle cells.

There is also variation in the time that a cell spends in each phase of the cell cycle. When fast-dividing mammalian cells are grown in culture outside the body under optimal growing conditions , the length of the cycle is approximately 24 hours. In rapidly dividing human cells with a hour cell cycle, the G 1 phase lasts approximately 11 hours. Interestingly, nuclear fission requires F-actin. This is reminiscent of animal cells in which F-actin-dependent mechanisms promote spindle positioning and orientation [reviewed in Sandquist et al.

The study strikingly showed that chromosome segregation is also fine to some degree. This might be also due to actin-dependent mechanisms as in bacterial cells in which chromosome segregation is driven by actin-like cytoskeleton.

It is also possible that the segregation system utilizes any nucleoplasmic factors such as Csi1, as a material that connects mitotic SPBs and kinetochores even in the absence of microtubules, because Csi1 has been shown to connect SPBs and centromeres constantly in interphase Hou et al. It should be noted that no specific systems have been so far identified that ensure the equal segregation of sister chromatids in eukaryotes besides spindle microtubules.

Currently, it is hard to completely rule out the possibility that very tiny residual microtubule seeds remain at SPBs even in the presence of the drug, as such tiny microtubule seeds might be able to connect SPBs and kinetochores clustered altogether at the mitotic onset. Once such attachments were made, kinetochore-mediated SPB separation might take place similar to the situation in Figure 3C to separate SPBs and segregate sister chromatids. It has been impossible to completely disrupt microtubules and inhibit regrowth by existing drugs; it would be intriguing to revisit these phenomena again when more effective drugs are invented in the future.

The evolutionary origin of meiosis has been discussed from the viewpoint of the phenomena for a long period, and one of the most reasonable ideas must be that meiosis was evolved from mitosis Simchen and Hugerat, Although meiosis is different from mitosis in many ways, one of the most essential characteristics in meiosis could be pairing of homologous chromosomes. Meiosis might have first evolved from mitosis through the acquisition of homolog pairing as an additional step Wilkins and Holliday, As the molecular mechanisms have been illuminated in the last decades, the idea is getting realistic as evidenced by the genes involved in key events in meiosis.

Most of the key events in meiosis appear to be conducted by meiosis-specific genes that are paralogous to those used in mitosis. Assuming that paralogous genes are generated via gene duplication in the long history of evolution, Spo11 S.

The meiotic cohesin Rec8 could likewise be originated from a duplicated copy of the mitotic cohesin Rad Those key factors might have defined the outline of meiosis as a newly acquired division system.

In addition to those copied genes, meiosis-specific genes whose ancestors are currently unknown are also created to fine-tune meiotic events to the current state. On the other hand, we also know that molecules or detailed molecular mechanisms in meiosis have been differentiated depending on species, although the whole system of meiosis per se is common among eukaryotes. The molecular mechanisms are thought to be fine-tuned in each organism depending on internal and external reasons such as the lifestyle and surrounding environment.

Considering similarities and differences among species and in between two types of divisions, we will be able to converge the divergent mechanisms to explore the ultimate origin in the future. MS conceived the framework of the entire manuscript. MS prepared the figures. All the authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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