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BIOL 1406 HCC-SW/Stafford Campus J.L. Marshall, Ph.D. Chapter 12- The Cell Cycle* *Lecture notes are to be used as a study guide only and do not represent the comprehensive information you will need to know for the exams. The Key Roles of Cell Division Living things can reproduce their own kind. The continuity of life is based on cell division (Figure 12.1). Cell division is important to reproduce new organisms and to replace dead cells (Figure 12.2 a - c). The cell division process is part of the cell cycle. A parent cell divides into two (2) daughter cells. The important aspect is the continuity of the passage of genetic information. Concept 12.1 : Most cell division results in genetically identical daughter cells Cell division is a complex process that ensures the passage of genetic information to daughter cells. Meiosis is a unique type of cell division that produces sperm and eggs. Cell division involves the duplication of DNA that is passed equally to two daughter cells. Cellular Organization of the Genetic Material The complete genetic information in a cell is called its genome. DNA is packaged into structures called chromosomes (Figure 12.3). A chromosome is DNA with associated proteins. Discrete units of genetic information that determines the traits of the individual is located on the chromosomes. Somatic cells are cells of the body. For humans somatic cells contain 46 chromosomes. Reproductive cells, gametes, sperm and eggs, for humans contain half as many, or 23 chromosomes. Distribution of Chromosomes During Eukaryotic Cell Division After DNA replication, and before cell division, the chromosomes condense. Each duplicated chromosome has two sister chromatids, which are joined copies of the original chromosome (Figure 12.4). Each sister chromatid has a centromere, a region containing specific DNA sequences where the sister chromatids are attached. Either side of the chromatid is referred to as the arm. As a result of cell division, each sister chromatid separates and moves to either side of the new cell (Figure 12.5). Mitosis is the division of the genetic material in the nucleus, which is immediately followed by cytokinesis, the division of the cytoplasm. One cell has become two (2), each the genetic equivalent of the parent cell. 1 BIOL 1406 HCC-SW/Stafford Campus J.L. Marshall, Ph.D. Concept 12.2 : The mitotic phase alternates with interphase in the cell cycle. In 1882 German anatomist Walther Flemming observed mitosis with dyes that he developed. Phases of the Cell Cycle The cell cycle consists of the mitotic (M) phase, which includes both mitosis and cytokinesis, which are shorter phases. A longer phase, called interphase, is much longer (Figure 12.6). Interphase is divided into three subphases: G1 phase (gap 1), S phase (“synthesis”), G2 (gap 2). The cell will reproduce its cellular components, like organelles, and only during S phase will it duplicate its chromosomes. Mitosis is broken down into five stages: prophase, prometaphase, metaphase, anaphase, and, telophase. Cytokinesis completes the mitotic phase (Figure 12.7). Phases of the Cell Cycle • Mitosis is conventionally divided into five phases – Prophase: chromatin condenses to form chromosomes (two sister chromatids) – Prometaphase: kinetochore microtubules attach to the kinetochore of the sister chromatids, nuclear membrane fragments – Metaphase: chromosomes line up in the middle of the cell – Anaphase: sister chromatids are pulled apart to opposite poles of the cell – Telophase: nucleus forms in each new cell, cell begins to divide in two • Cytokinesis overlaps the latter stages of mitosis: cells are physically separated The Mitotic Spindle: A Closer Look The mitotic spindle forms during prophase, and consists of microtubules and proteins. In an animal cell, the spindle microtubules assemble at the centromere. By the end of prometaphase, two centrosomes, one at each pole of the spindle, are at opposite ends of the cell. An aster, a radial array of short microtubules, extends from each centrosome. Each sister chromatid has a kinetochore, a structure of proteins associated with specific sections of chromosomal DNA at each centromere. When a microtubule attaches to a kinetochore, it moves the sister chromatid towards each pole. At metaphase, the chromosomes are moved to the “equator” of the cell, defining the metaphase plate (Figure 12.8). Anaphase is the separation of the sister chromatids. Once each sister chromatid separates, they are full-fledged chromosomes. At the end of 2 BIOL 1406 HCC-SW/Stafford Campus J.L. Marshall, Ph.D. anaphase, the nuclei begin to reform during telophase. Cytokinesis begins at the end of anaphase, or telophase, and the two cells separate. Cytokinesis: A Closer Look In animal cells, cytokinesis occurs by a process known as cleavage. The first sign is a cleavage furrow (Figure 12.10a). The cleavage furrow deepens until the cell becomes two cells. In plant cells, there is no cleavage furrow, but a cell plate (Figure 12.10b and Figure 12.11). Binary Fission in Bacteria Bacteria and Archaea divide by a process called binary fission (Figure 12.12). This is a type of asexual reproduction. Bacteria have a singular circular chromosome with one copy of each gene. E. coli has been used as the model organism to understand cell replication among prokaryotes. The Evolution of Mitosis There are some proteins that are involved in prokaryotic cell replication that are used in eukaryotic cell replication. Over the course of evolution, the process of cell replication in prokaryotes evolved to eukaryotes (Figure 12.13). Concept 12.3 : The eukaryotic cell cycle is regulated by a molecular control system The frequency of cell division varies with the cell type. Human skin cells divide frequently, but human nerve cells do not divide in a mature human. The cell cycle differences result from regulation at the molecular level. Evidence for Cytoplasmic Signals The cell cycle is driven by specific signaling molecules present in the cytoplasm (Figure 12.14, Figure 12.16). 3 BIOL 1406 HCC-SW/Stafford Campus J.L. Marshall, Ph.D. The Cell Cycle Control System The sequential events of the cell cycle is directed by a distinct cell cycle control system, a cyclically operating set of molecules in the cell that both triggers and coordinates key events in the cell cycle (Figure 12.15). The cell cycle control system proceeds on its own. The cell cycle is regulated at certain checkpoints by both internal and external signals. A checkpoint in the cell cycle is a control point where stop and go-ahead signals can regulate the cycle. The signals report whether crucial cellular processes that should have occurred by that point have in fact been completed correctly and thus whether or not the cell cycle should proceed. Three major check points are found in the G1, G2, and M phases. The G1 checkpoint in mammalian cells seems to be the most important. If the “go-ahead” signal is not received at G1 the cell will exit the cell cycle and switch to a non-dividing state called G0 phase (Figure 12.17). The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases Rhythmic fluctuations in the regulatory proteins pace the cell cycle. The two main regulatory proteins are protein kinases and cyclins. For a protein kinase to be active it must be attached to a cyclin, thus they are called cyclin-dependent kinases, or Cdks. The fluctuating activities of different cyclin-Cdk complexes are of major importance in controlling all the stages of the cell cycle. Stop and Go Signs: Internal and External Signals at the Checkpoints There are many external factors, both chemical and physical, that can influence cell division. There are a variety of different growth factors that stimulates cells to divide. The effect of external physical factors on cell division is clearly seen in density-dependent inhibition, a phenomenon in which cells stop dividing after a certain point (Figure 12.19a). Most animal cells exhibit anchorage dependence, meaning, in order to divide they must be attached to a surface. Cancer cell exhibit neither density-dependent inhibition nor anchorage dependence (Figure 12.19b). Loss of Cell Cycle Controls in Cancer Cells Cancer cells do not follow the normal cell cycle. They divide excessively and invade other tissues. Cancer cells do not respond to the normal checkpoints. Cancer cells evade the normal triggers that cause apoptosis when something goes wrong. When normal cells become cancerous, they undergo a transformation. If left uncheck by the body’s immune system, the cancer cells can form a tumor. Some tumors are benign, and can be easily removed. Some tumors are malignant, and can spread and cause further tissue damage. Once a tumor is malignant, the person is said to have cancer (Figure 12.20). The spread of cancer cells away from their original site is called metastasis. 4