The Eukaryotic Cell Cycle

• Over 10,000,000,000,000! Researchers estimate the adult human body contains somewhere between 10 trillion to 50 trillion cells. It is almost an incomprehensible number. Even more amazing is the accuracy of the process that produces these cells.

• After a human sperm and egg unite, the fertilized egg goes through a long series of cell divisions to produce an adult with over 10 trillion cells.

The Eukaryotic Cell Cycle

Life is a continuum in which new living cells are formed by the division of pre-existing cells. The Latin axiom Omnis cellula e cellula, meaning “Every cell from a cell,” was first proposed in 1858 by a German pathologist, Rudolf Virchow.

From an evolutionary perspective, cell division has a very ancient origin. All living organisms, from unicellular bacteria to multicellular plants and animals, have been produced by a series of repeated rounds of cell growth and division extending back to the beginnings of life nearly 4 billion years ago.

The Eukaryotic Cell Cycle

• Cell division is a process that involves remarkable accuracy and precise timing. A cell must be able to sense when conditions are appropriate for division to occur and then orchestrate a series of events that will ensure the production of healthy new cells.

• A key issue is that the chromosomes must be properly replicated and sorted to new daughter cells.

Eukaryotic Chromosomes Are Inherited in Sets and Occur in Homologous Pairs

• To understand the chromosomal composition

of cells and the behavior of chromosomes during cell division, scientists observe cells and chromosomes with the use of microscopes.

Cytogenetics

• Cytogenetics is the field of genetics that involves the microscopic examination of chromosomes and cell division. When a cell prepares to divide, the chromosomes become more tightly compacted, a process that decreases their apparent length and increases their diameter. A consequence of this compaction is that distinctive shapes and numbers of chromosomes become visible with a light microscope.

A karyotype reveals :

1.the number, 2. size, and

3. form of chromosomes found within an actively dividing cell.

Microscopic Examination of Chromosomes

Sets of Chromosomes

• What type of information is learned from a karyotype? • By studying the karyotypes of many species, scientists have

discovered that eukaryotic chromosomes occur in sets. • Each set is composed of several different types of chromosomes.

For example, one set of human chromosomes contains 23 different types of chromosomes (see Figure 15.1).

• By convention, the chromosomes are numbered according to size, with the largest chromosomes having the smallest numbers. For example, human chromosomes 1, 2, and 3 are relatively large, whereas 21 and 22 are the two smallest.

• This numbering system does not apply to the sex chromosomes, which determine the sex of the individual. Sex chromosomes in humans are designated with the letters X and Y. The chromosomes that are not sex chromosomes are called autosomes. Humans have 22 different types of autosomes.

• A second feature of many eukaryotic species is that most cells contain two sets of chromosomes. The karyotype shown in Figure 15.1 contains two sets of chromosomes, with 23 different chromosomes in each set. Therefore, this human cellcontains a total of 46 chromosomes. A person’s cells have 46 chromosomes each because the individual inherited one setfrom the father and one set from the mother. When the cells of an organism carry two sets of chromosomes, that organism is said to be diploid. Geneticists use the letter n to represent a set of chromosomes, so diploid organisms are referred to as 2n.For example, humans are 2n, where n 23. Most human cells are diploid. An exception involves gametes, namely, sperm and egg cells. Gametes are haploid, or 1n, which means they contain one set of chromosomes.

Homologous Pairs of Chromosomes

• When an organism is diploid, the members of a pair of chromosomes are called homologues (see inset to Figure 15.1). The term homology refers to any similarity that is due to common ancestry. Pairs of homologous chromosomes are evolutionarily derived from the same chromosome.

• However, homologous chromosomes are not usually identical to each other because over many generations they have accumulated some genetic changes that make them distinct.

The phases of the cell cycle are G (first gap), S (synthesis of DNA, the genetic material), G (second gap), and M phase (mitosis and cytokinesis). The G1 and G phases were originally described as gap phases to indicate a pause in activity between DNA synthesis and mitosis. However, we now know these are critical phases of the cell cycle. In actively dividing cells, the G2, S, and G phases are collectively known as interphase.

The Cell Cycle Is a Series of Phases That Lead to Cell Division

During interphase, the cell grows and copies its chromosomes in preparation for cell division. Alternatively, cells may exit the cell cycle and remain for long periods of time in a phase called G0(G zero). The G0 phase is an alternative to proceeding through G1. A cell in the G0 phase has postponed making a decision to divide or, in the case of terminally differentiated cells (such as nerve cells in an adult animal), has made a decision to never divide again. G0 is a nondividing phase.

The eukaryotic cell cycle thr

The G1 phase is a period in a cell’s life when it may become committed to divide. Depending on the environmental conditions and the presence of signaling molecules, a cell in the G1phase may accumulate molecular changes that cause it to progress through the rest of the cell cycle. Cell growth typically occurs during the G1 phase.

G2Phase During the G2 phase, a cell synthesizes proteins that are necessary for chromosome sorting and cell division. This prepares the cell for the last phase of the cell cycle. Some cell growth may occur.

S Phase During the S phase, the chromosomes are replicated. After replication, the two copies are still joined to each other and referred to as a pair of sister chromatids. When S phase is completed, a cell actually has twice as many chromatids as the number of chromosomes in the G1 phase. For example, a human cell in the G1 phase has 46 distinct chromosomes, whereas the same cell in G2 would have 46 pairs of sister chromatids, for a total of 92 chromatids.

M Phase The first part of M phase is mitosis. The purpose of

mitosis is to divide one cell nucleus into two nuclei, distributing the duplicated chromosomes so that each daughter cell will receive the same complement of chromosomes.

A human cell in the G2 phase has 92 chromatids, which are found in 46 pairs. During mitosis, these pairs of chromatids are separated and sorted so that each daughter cell will receive 46 chromosomes. Mitosis is the name given to this sorting process.

In most cases, mitosis is followed by cytokinesis, which is the division of the cytoplasm to produce two distinct daughter cells.

The length of the cell cycle

The length of the cell cycle varies considerably among different cell types, ranging from several minutes in quickly growing embryos to several months in slow-growing adult cells.

For fast-dividing mammalian cells in adults, the length of the cycle is typically 24 hours. The various phases within the cell cycle also vary in length. G is often the longest and also the most variable phase, and M phase is the shortest.

For a cell that divides in 24 hours, the following lengths of time for each phase are typical: G1 phase: 11 hours S phase: 8 hours G2 phase: 4 hours M phase: 1 hour

Control of Cell Division

What factors determine whether or not a cell will divide?

First, the determination to divide is based on external factors, such as environmental conditions and signaling molecules.

Second, internal controls affect cell division. These include cell cycle control molecules and checkpoints, as we will discuss next.

The Cell Cycle Is Controlled by Checkpoint Proteins

• The progression through the cell cycle is a process that is highly regulated to ensure that the nuclear genome is intact and that the conditions are appropriate for a cell to divide. This is necessary to minimize the occurrence of mutations, which could have harmful effects and potentially lead to cancer.

• Proteins called cyclins and cyclin-dependent kinases (cdks) are responsible for advancing a cell through the phases of the cell cycle. Cyclins are so named because their amount varies throughout the cell cycle. To be active, the kinases controlling the cell cycle must bind to (are dependent on) a cyclin. The number of different types of cyclins and cdks varies from species to species.

Checkpoints in the cell cycle

Study of Oocyte Maturation Led to the Identification of Cyclins and Cyclin-Dependent Kinases (Yoshio Masui and Clement Markert)

At the time of their work, researchers had already determined that frog oocytes naturally become dormant in the G2 phase of the cell cycle for up to eight months (Figure 15.5). During mating season, female frogs produce a hormone called progesterone. After progesterone binds to receptors in dormant egg cells, they progress from G2 to the beginning of M phase, where the chromosomes condense and become visible under the microscope. This phenomenon is called maturation. When a sperm fertilizes the egg, M phase is completed, and the zygote continues to undergo cellular divisions.

Masui’s Experiment

Masui’s Experiment (1)

Masui’s Experiment (2)

Cancer Cancer is a disease of multicellular organisms characterized

by uncontrolled cell division. Worldwide, cancer is the second leading cause of death in

humans, exceeded only by heart disease. In the United States, approximately 1.5 million people are diagnosed with cancer each year; over 0.5 million will die from the disease. Overall, about one in four Americans will die from cancer.

Most cancers, though, perhaps 90%, do not involve genetic changes that are passed from parent to offspring. Rather, cancer is usually an acquired condition that typically occurs later in life. At least 80% of all human cancers are related to exposure to carcinogens, agents that increase the likelihood of developing cancer.

Most carcinogens, such as UV light and certain chemicals in cigarette smoke, are mutagens that promote genetic changes in somatic cells. These DNA alterations can lead to effects on gene expression that ultimately affect cell division and thereby lead to cancer.

The progression cancer

How does cancer occur? In most cases, the development of cancer is a multistep process ( Figure 14.10).

Cancers originate from a single cell. This single cell and its lineage of daughter cells undergo a series of mutations that causes the cells to grow abnormally. At an early stage, the cells form a tumor, which is an overgrowth of cells.

For most types of cancer, a tumor begins as a precancerous or benign growth. Such tumors do not invade adjacent tissues and do not spread throughout the body.

This may be followed by additional mutations that cause some cells in the tumor to lose their normal growth regulation and become malignant. At this stage, the individual has cancer.

Cancerous tumors invade healthy tissues and may spread through the bloodstream or surrounding body fluids, a process called metastasis. If left untreated, malignant cells will cause the death of the organism.

Over the past few decades, researchers have identified many genes that promote cancer when they are mutant. By comparing the function of each mutant gene with the corresponding nonmutant gene found in healthy cells, these genes have been placed into two categories.

In some cases, a mutation causes a gene to be overactive—have an abnormally high level of expression. This overactivity contributes to the uncontrolled cell growth that is observed in cancer cells. This type of mutant gene is called an oncogene.

Alternatively, when a tumor-suppressor gene is normal (that is, not mutant), it encodes a protein that helps to prevents cancer. However, when a mutation eliminates its function, cancer may occur.

Thus, the two categories of cancer- causing genes are based on the effects of mutations.

1. Oncogenes are the result of mutations that cause overactivity, 2. whereas cancer-causing mutations in tumor- suppressor genes are due to a loss of activity.

Oncogenes Cause the Overactivity of Proteins That Promote Cell Division

Over the past four decades, researchers have identified many oncogenes. A large number of oncogenes encode proteins that function in cell growth signaling pathways. Cell division is regulated, in part, by growth factors, which are a type of hormone that regulates cell division.

A growth factor binds to a receptor, which results in receptor activation ( Figure 14.11). This stimulates an intracellular signal transduction pathway that activates transcription factors. In this way, the transcription of specific genes is activated in response to a growth factor. After they are made, the gene products promote cell division.

Oncogenes Cause the Overactivity of Proteins That Promote Cell Division

Eukaryotic species produce many different growth factors that play a role in cell division. Likewise, cells have several different types of signal transduction pathways that respond to these molecules and promote cell division. Mutations in the genes that produce these signaling proteins can change them into oncogenes ( Table 14.6).

Oncogenes result in an abnormally high level of activity in these proteins, which can include growth factor receptors, intracellular signaling proteins, and transcription factors.