Biology 130 Molecular Biology and Genetics Chromosomes dividing

Biology 130 – Molecular Biology and Genetics Chromosomes dividing during Cell division Kandinsky – Several Circles

Biology 130 – Molecular Biology and Genetics Knox College Winter 2007 Instructors: Matt Jones-Rhoades Stuart Allison SMC B 110 SMC B 210 x 7477 x 7185 email: mjrhoade email: sallison Lab Coordinator: Ramiya Venigalla, SMC B 113, x 7386, email: rvenigal Office Hours: Jones-Rhoades: Tues 2 nd Period, Wed 4 th Period, Fri 6 th Period. Allison: MWTh. F 3 rd Period; Venigalla – MW 12: 30 -1: 30 Lecture: SMAC A 110 MWF 2 nd Period Lab: SMAC B 121 Textbooks: Campbell and Reece. 2011. Biology 9 th Ed. Benjamin Cummings. Ridley. 2006. Genome. Perennial. Course Webpage: http: //courses. knox. edu/bio 130

Cell Division • Unicellular organisms – Reproduce by cell division • Multicellular organisms depend on cell division for – Development from a fertilized cell – Growth – Repair • The cell division process – Is an integral part of the cell cycle

Cell theory of life • ‘Where a cell exists, there must have been a preexisting cell, just as the animal arises only from an animal and the plant only from a plant. ’ - Rudolf Virchow, 1855

• Cell division results in genetically identical daughter cells • Cells duplicate their genetic material before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA • A cell’s endowment of DNA, its genetic information, is called its genome • The DNA molecules in a cell are packaged into chromosomes

Chromosomes • Eukaryotic chromosomes – Consist of chromatin, a complex of DNA and protein that condenses during cell division • In animals – Somatic cells have two sets of chromosomes – Gametes have one set of chromosomes • In preparation for cell division – DNA is replicated and the chromosomes condense

Cell Division • Eukaryotic cell division consists of – Mitosis, the division of the nucleus – Cytokinesis, the division of the cytoplasm • In meiosis – Sex cells are produced after a reduction in chromosome number

The cell cycle consists of the mitotic phase and interphase. Interphase can be broken down into three phases – G 1, S, and G 2.

The Cell Cycle • We typically divide interphase into three phases – the G 1 phase (for Gap 1), the S phase (for synthesis), and G 2 phase (for gap 2). • The cell only duplicates its chromosomes (DNA) during the S synthesis phase. Thus a cell grows (G 1), continues to grow as it synthesizes DNA and duplicates chromosomes (S), grows more and completes preparations for cell division (G 2) and then divides (M). • Daughter cells then repeat the cycle – potentially infinitely.

Red spotted newt

• By late interphase, the chromosomes have been duplicated but are loosely packed. • The centrosomes have been duplicated and begin to organize microtubules into an aster (“star”). Fig. 12. 5 a

• In prophase, the chromosomes are tightly coiled, with sister chromatids joined together. • The nucleoli disappear. • The mitotic spindle begins to form and appears to push the centrosomes away from each other toward opposite ends (poles) of the cell. Fig. 12. 5 b

• During prometaphase, the nuclear envelope fragments and microtubules from the spindle interact with the chromosomes. • Microtubules from one pole attach to one of two kinetochores, special regions of the centromere, while microtubules from the other pole attach to the other kinetochore. Fig. 12. 5 c

• The spindle fibers push the sister chromatids until they are all arranged at the metaphase plate, an imaginary plane equidistant between the poles, defining metaphase. Fig. 12. 5 d

• At anaphase, the centromeres divide, separating the sister chromatids. • Each is now pulled toward the pole to which it is attached by spindle fibers. • By the end, the two poles have equivalent collections of chromosomes. Fig. 12. 5 e

• At telophase, the cell continues to elongate as free spindle fibers from each centrosome push off each other. • Two nuclei begin to form, surrounded by the fragments of the parent’s nuclear envelope. • Chromatin becomes less tightly coiled. • Cytokinesis, division of the cytoplasm, begins. Fig. 12. 5 f

Figure 12. 6 The mitotic spindle at metaphase

Movement of chromosomes – In this model a chromosome tracks along a microtubule as the microtubule depolymerizes at its kinetochore end, releasing tubulin subunits – Pac-man mechanism.

Movement of chromosomes - ‘Reeling in’ vs ‘Pac-man’

• Nonkinetichore (polar) microtubules are responsible for lengthening the cell along the axis defined by the poles. – These microtubules interdigitate across the metaphase plate. – During anaphase motor proteins push microtubules from opposite sides away from each other. – At the same time, the addition of new tubulin monomers extends their length.

Bacterial cell division

Dinoflagellate Diatoms

A molecular control system drives the cell cycle • The cell cycle appears to be driven by specific chemical signals in the cytoplasm. – Fusion of an S phase cell and a G 1 phase cell induces the G 1 nucleus to start S phase. – Fusion of a cell in mitosis with one in interphase induces the second cell to enter mitosis. Fig. 12

• The distinct events of the cell cycle are directed by a cell cycle control system. – These molecules trigger and coordinate key events in the cell cycle. – The control cycle has a built-in clock, but it is also regulated by external adjustments and internal controls. Fig. 12. 13

• A checkpoint in the cell cycle is a critical control point where stop and go signals regulate the cycle. – Many signals registered at checkpoints come from cellular surveillance mechanisms. – These indicate whether key cellular processes have been completed correctly. – Checkpoints also register signals from outside the cell. • Three major checkpoints are found in the G 1, G 2, and M phases.

• For many cells, the G 1 checkpoint, the restriction point in mammalian cells, is the most important. – If the cell receives a go-ahead signal, it usually completes the cell cycle and divides. – If it does not receive a go-ahead signal, the cell exits the cycle and switches to a nondividing state, the G 0 phase. • Most human cells are in this phase. • Liver cells can be “called back” to the cell cycle by external cues (growth factors), but highly specialized nerve and muscle cells never divide.

• Rhythmic fluctuations in the abundance and activity of control molecules pace the cell cycle. – Some molecules are protein kinases that activate or deactivate other proteins by phosphorylating them. • The levels of these kinases are present in constant amounts, but these kinases require a second protein, a cyclin, to become activated. – Levels of cyclin proteins fluctuate cyclically. – The complex of kinases and cyclin forms cyclindependent kinases (Cdks).

• Cyclin levels rise sharply throughout interphase, then fall abruptly during mitosis. • Peaks in the activity of one cyclin-Cdk complex, MPF, correspond to peaks in cyclin concentration. Fig. 12. 14 a

• MPF (“maturation-promoting factor” or “Mphase-promoting-factor”) triggers the cell’s passage past the G 2 checkpoint to the M phase. – MPF promotes mitosis by phosphorylating a variety of other protein kinases. – MPF stimulates fragmentation of the nuclear envelope. – It also triggers the breakdown of cyclin, dropping cyclin and MPF levels during mitosis and inactivating MPF. Fig. 12. 14 b

• The key G 1 checkpoint is regulated by at least three Cdk proteins and several cyclins. • Similar mechanisms are also involved in driving the cell cycle past the M phase checkpoint.