Chapter 3

Metaphase Checkpoint

pass if all chromosomes are attached to mitotic spindle

G2 checkpoint

pass if cell size is adequate and chromosome replication is successfully completed

G1 Checkpoint

pass if cell size is adequate, nutrient availability is sufficient, and growth factors (signals from other cells) are present

Recombination nodules

protein assemblies formed on the synaptonemal complex that mark the points of crossover events and mediate the multistep process of genetic recombination between non-sister chromatids

Pseudoautosomal Regions (PARs)

Sex chromosomes differ from pairs of autosomal chromosomes in that the X chromosome and Y chromosome have very few genes in common. Even so, the X and Y chromosomes of males align as homologs in prophase I. This synapsis is accomplished with the aid of pseudoautosomal regions (PARs) on the two types of sex chromosomes. The term pseudoautosomal means "false autosomal"; a PAR is a segment of homology between otherwise different chromosomes. PARs are like homologous sequences carried on authentic autosomes. The pattern of inheritance of a pseudoautosomal region would be indistinguishable from the pattern of autosomal inheritance, as a consequence of the homology.

G0 Phase

Terminal differentiation and arrest of cell division.

Prophase I: Zygotene

chromosomes continue to condense and homologous chromosomes enter synapsis. Synaptonemal complex forms between homologs.

Prophase I: Leptotene

chromosomes start to condense but not enough that they can be seen. Centrosomes begin to migrate to opposite poles and asters of microtubule spindle fibers are produced from the centrosome.

Nondisjunction

Error in meiosis in which homologous chromosomes fail to separate.

Interphase

G1, S, G2

TDF (testis determining factor)

Gene on Y chromosome that initiates male development Alternatively SRY Gene

Anaphase I

Homologous chrmosomes move to the oppisite poles of the cell.

Karyokinesis

Homologous chromosomes align on opposite sides of the metaphase plate in metaphase I. Kinetochore microtubules from one centrosome attach to the kinetochores of both sister chromatids of one chromosome. Meanwhile, kinetochore microtubules from the other centrosome attach to the kinetochores of the sister chromatids of the homolog. Karyokinesis takes place in anaphase I as homologous chromosomes separate from one another and are dragged to opposite poles of the cell (see Figure 3.10). The sister chromatids of each chromosome remain firmly joined by cohesin. Nuclear membrane re-formation takes place in telophase I, when a haploid set of chromosomes are enclosed at each pole of the cell. Cytokinesis follows the completion of telophase I.

Sister Chromatids

Identical copies of a chromosome; full sets of these are created during the S subphase of interphase.

Barr body

Inactivated X chromosome

Centrosomes

Microtubule-organizing centers that help to form and organize the mitotic spindle during mitosis

Meiosis I

Prophase I (leptotene stage, zygotene stage, pachytene stage, diplotene stage, and diakinesis stage), Metaphase I, Anaphase I, Telophase I 1. Homologous chromosome pairing 2. Crossing over between homologous chromosomes 3. Segregation (separation) of the homologous chromosomes that reduces chromosomes to the haploid number

random X-inactivation (Lyon hypothesis)

Proposed by Mary Lyon in the mid-20th century, the process of randomly inactivating one copy of the X chromosome in each mammalian female nucleus early in zygotic development.

X-inactivation

Random X inactivation requires a gene on the X chromosome called the X-inactivation-specific transcript (XIST) that encodes a large RNA molecule. XIST RNA spreads out from the gene, "painting" the X chromosome as it accumulates. X chromosomes that are painted with XIST RNA have all, or nearly all, of their genes silenced. The XIST gene is expressed on only one of the two X chromosomes, and its RNA accumulates only on the chromosome transcribing the gene; it does not spread to the homologous X chromosome. In other words, XIST acts only in cis (on the same chromosome) but not in trans (on the homologous chromosome). Examination of inactivated chromosomes in the nucleus detects XIST RNA coating the Barr body in a nucleus.

G1 Phase

Active gene expression and cell activity; preparation for DNA synthesis

Anaphase A Disjunction

Anaphase A begins abruptly with two simultaneous events. First, the enzyme separase initiates cleavage of polypeptides in cohesin, thus breaking down the connection between sister chromatids. Second, kinetochore microtubules begin to depolymerize at their (+)(+) ends to initiate chromosome movement toward the centrioles. The separation of sister chromatids in anaphase A is called chromosome disjunction. As anaphase progresses, sister chromatids complete their disjunction and eventually congregate around the centrosomes at the cell poles.

Aster

3 kinds of spindle fibers emanate from the centrosomes. 1. Kinetochore microtubules embed in the protein complex called the kinetochore (described shortly) that assembles at the centromere of each chromatid. Kinetochore microtubules are responsible for chromosome movement during cell division. 2. Nonkinetochore microtubules extend toward each other from the two polar centrosomes and overlap to help elongate and stabilize the cell during division. 3. Astral microtubules grow toward the membrane of the cell, where they attach and contribute to cell stability.

Hemizygous

A gene present on the X chromosome that is expressed in males in both the recessive and dominant condition

Telophase II and Cytokinesis (Meiosis)

A nuclear envelope forms around each set of chromosomes. the cytoplasm divides.

Kinetochore

A specialized region on the centromere that links each sister chromatid to the mitotic spindle.

Centromere

Area where the chromatids of a chromosome are attached

Prophase I: Pachytene

Chromosome condensation is partially complete and crossing over occurs between nonsister chromatid. Nuclear envelope begins to break down. Chromosome condensation continues in pachytene, and sister chromatids of each chromosome can be visually distinguished by light microscopy. At this stage, the paired homologs are called a tetrad in recognition of the four chromatids that are microscopically visible in each homologous pair. Within the central element of the synaptonemal complex, new structures called recombination nodules appear at intervals. Recombination nodules play a pivotal role in crossing over of genetic material between nonsister chromatids of homologous chromosomes. The number of recombination nodules correlates closely with the average number of crossover events along each homologous chromosome arm. Two important observations have been made about recombination nodules. First, their appearance and location within the synaptonemal complex is coincident with the timing and location of crossing over; and second, recombination nodules seem to be present in organisms that undergo crossing over and absent in those that do not. Cell biologists have concluded that recombination nodules are aggregations of enzymes and proteins that are needed to carry out genetic exchange between the nonsister chromatids of homologous chromosomes during pachytene. Later chapters discuss the genetic consequences of crossing over (Chapter 5) and the molecular processes of crossing over (Chapter 11).

chromosome vs chromatid

Chromosome is 2 chromatids together with a centromere in the middle of the chromatids and chromosome. .

Prophase

Chromosomes become visable, nuclear envelop dissolves, spindle forms

Telophase I and Cytokinesis (Meiosis)

Chromosomes gather at the poles of the cells. the cytoplasm divides.

Metaphase II

Chromosomes line up at the equator.

Metaphase

Chromosomes line up in the middle of the cell

Prophase I: Diplotene

Crossing over is completed. Synaptonemal complex dissolves. Chiasmata continues linking the cross overs. Nuclear envelope continues to break down.

S Phase

DNA replication and chromosome duplication

Motor proteins

Move chromosomes and other cell structures along microtubules

Nonsister Chromatids

Nonsister chromatids are chromatids belonging to different members of a homologous pair of chromosomes. The binding of nonsister chromatids by a synaptonemal complex draws the homologs into close contact (synapsis). The synaptonemal complex contains two lateral elements, each consisting of proteins adhered to a chromatid from a different member of a pair of homologous chromosomes, as well as a central element that joins the lateral elements. The function of the synaptonemal complex is to properly align homologous chromosomes before their separation and then to facilitate recombination between homologous chromosomes.

spindle fiber microtubules

Organize and separate chromosomes Are polar - end at centrosome + end away from centrosome

Synapsis

Pairing of homologous chromosomes.

Telophase and Cytokinesis

Pairs arrives at poles and cell is pinched apart, separating into two cells. In telophase, nuclear membranes begin to reassemble around the chromosomes gathered at each pole, eventually enclosing the chromosomes in nuclear envelopes. Chromosome decondensation begins and ultimately returns chromosomes to their diffuse interphase state. At the same time, microtubules disassemble. As telophase comes to an end, two identical nuclei are observed within a single elongated cell that is about to be divided into two daughter cells by the process of cytokinesis. In animal cells, a contractile ring composed of actin microfilaments creates a cleavage furrow around the circumference of the cell; the contractile ring pinches the cell in two (Figure 3.5). In plant cells, cytokinesis entails the construction of new cell walls near the cellular midline. In both plant and animal cells, cytokinesis divides the cytoplasmic fluid and organelles.

S phase checkpoint

Pass if DNA replication is complete and has been screened to remove base-pair mismatch or error

Anaphase

Phase of mitosis in which the chromosomes separate and move to opposite ends of the cell

G2 Phase

Preparation for cell division

Crossing over

Process in which homologous chromosomes exchange portions of their chromatids during meiosis.

Chaismata

The chromosomes continue to condense in diplotene as the synaptonemal complex begins to dissolve. The dissolution allows homologs to pull apart slightly, revealing contact points between nonsister chromatids. These contact points are called chiasmata (singular: chiasma), and they are located along chromosomes where crossing over has occurred. Chiasmata mark the locations of DNA-strand exchange between nonsister chromatids of homologous chromosomes. Cohesin protein is present between sister chromatids to resist the pulling forces of kinetochore microtubules (Figure 3.12). In diakinesis, kinetochore microtubules actively move synapsed chromosome pairs toward the metaphase plate, where the homologs will align side by side. The chiasmata between homologous chromosomes are resolved in late prophase I so that the homologs can be aligned in metaphase I. This process of resolving the contacts between homologs is critical to the completion of recombination between homologous chromosomes.

Prophase I: Diakinesis

The meiotic spindle is well established, with bundles of kinetochore microtubules tethering homologous chromosomes of tetrads to opposite poles. The nuclear envelope is fully degraded. Tetrads are moved toward the middle of the cell.

Anaphase B

The next part of anaphase, anaphase B, is characterized by the polymerization of polar microtubules that extends their length and causes the cell to take on an oblong shape. The oblong shape facilitates cytokinesis at the end of telophase, which leads to the formation of two daughter cells.

X/autosome ratio (X/A ratio)

The ratio of X chromosomes to a pair of autosomes. Used in Drosophila as the mechanism of sex determination.

Prometaphase

The second stage of mitosis, in which the nuclear envelope fragments and the spindle microtubules attach to the kinetochores of the chromosomes.

Meiosis Generates Mendelian Ratios

The separation of homologous chromosomes and sister chromatids in meiosis constitutes the mechanical basis of Mendel's laws of segregation and independent assortment. The connection between meiosis and Mendelian hereditary principles was first suggested, independently, by Walter Sutton and Theodor Boveri in 1903. Based on microscopic observations of chromosomes during meiosis, Sutton and Boveri proposed two important ideas. First, meiosis was the process generating Mendel's rules of heredity; and second, genes were located on chromosomes. Over the next 2 decades, work on numerous species proved these hypotheses to be correct. We can understand segregation by following a pair of homologous chromosomes through meiosis in a heterozygous organism. Figure 3.15 illustrates meiosis in a pea plant with the heterozygous Gg genotype Recall that Mendel's law of segregation predicts that one-half (50%) of the gametes produced by a heterozygote will contain G and the remaining one-half will contain g. How does meiosis generate this outcome? DNA replication in S phase creates identical sister chromatids for each chromosome. At metaphase I, the homologs align on opposite sides of the metaphase plate; and at anaphase I, the homologs separate from one another. This movement segregates the chromosome composed of two G-bearing chromatids from the chromosome bearing the two g-containing chromatids. Following these cells through to the separation of sister chromatids in meiosis II, we find that among the four gametes are two containing the G allele and two containing g. This outcome explains the 1:1 ratio of alleles that the law of segregation predicts for gametes of a heterozygous organism. The mechanistic basis of Mendel's law of independent assortment is illustrated in Figure 3.16 for a GgRr dihybrid pea plant. Recall that this law of heredity predicts that a dihybrid organism should produce four genetically different gametes at a frequency of one-quarter (25%) each. Figure 3.16 Meiosis and the law of independent assortment. Assessing the results of meiosis in numerous cells with the GgRr genotype, four genetically different gametes, GR, Gr, gR, and gr are produced at frequencies of 25% each.

Z/W system

The sex chromosome inheritance system in species in which the male is homogametic (ZZ) and the female is heterogametic (ZW).

Sister Chromatid Cohesion and Separation

The tension created by the pull of kinetochore microtubules is balanced by this. The tension created by the pull of kinetochore microtubules is balanced by a companion process known as sister chromatid cohesion. Sister chromatid cohesion is produced by the protein cohesin that localizes between the sister chromatids and holds them together to resist the pull of kinetochore microtubules (Figure 3.4). Cohesin is a four-subunit protein; its central component is a polypeptide produced by the gene Scc1 for "sister chromatid cohesion." Cohesin coats sister chromatids along their entire length but is most concentrated near centromeres, where the pull of microtubules is greatest. As microtubules move chromosomes toward the midline of the cell, cohesin helps keep the sister chromatids together, to ensure proper chromosome positioning and to prevent their premature separation. Figure 3.4 Sister chromatid cohesion and separation. Cohesin protein induces cohesion between sister chromatids (a) and (b). At anaphase (c), separase protein digests cohesin and allows sister chromatids to separate.

synaptonemal complex

proteins that hold together homologous chromosomes. Synapsis initiates this. Trilayer protein structure that maintains synapsis by tightly binding NONHOMOLOGOUS chromatids of homologous chromosomes to one another Nonsister chromatids are chromatids belonging to different members of a homologous pair of chromosomes. The binding of nonsister chromatids by a synaptonemal complex draws the homologs into close contact (synapsis). The synaptonemal complex contains two lateral elements, each consisting of proteins adhered to a chromatid from a different member of a pair of homologous chromosomes, as well as a central element that joins the lateral elements. The function of the synaptonemal complex is to properly align homologous chromosomes before their separation and then to facilitate recombination between homologous chromosomes.

SRY gene

sex determining region of the Y chromosome, lack = females

Anaphase II

sister chromatids separate

Metaphase I

tetrads line up in the middle of the cell Chaismata linking nonsister chromatids are broken.

Prophase II

the nuclear envelope breaks down and the spindle apparatus forms