Cellular Reproduction

Cellular Reproduction

1. Cell Cycle

   • M Phase= mitosis (~1hr) and cytokinesis
     • proteolysis= destruction of mitotic cyclins= exit mitosis= enter new cell cycle
     • 1. Prophase: form mitotic chrom= 2 chromatids--compaction due to condensin protein and topoisomerase II--DNA of each chrom has cohesin, connects 2 sister DNA mols.
       • centromere: binding site for protein
       • Kinetochores: outer surface of centromere. site where chrom. attach to microtubule of mitotic spindle.
       • centrosome= microtubule-organizing structure. mitotic spindle=made of microtubule. centrosome cycle= centrioles are duplicated
         • centrosomes move apart and use motor proteins to organize microtubules that make mitotic spindle. in animals= aaster around centrosome
     • 1A. prometaphase: mitotic spindle formed and chroms. move to center of cell by microtubules grow around chrom. one kinetochore.
     • 2. Metaphase: chrom align at spindle equator. tubulin flux: incorporates subunits at kinetochorse of chromosomal mts and added/lost at equatorial ends of polar mts.
       • Types of Microtubules: Astral, Chromosomal (move chroms to poles) and Polar (maintain spindle integrity)
     • 3. Anaphase: sister chromatids split and move apart. Movmt of chrom to pole= Anaphase A. microtubules elongateand poles move in opp dir.= Ana. B
       • Proteolysis (IRREVERSIBLE): APC (anaphase promoting complex) activated b/w M and A and marks Securin (anaphase inhibitor) for destruction. Secruin destruction= Separase activation which cleaves Cohesin
       • Destruction of cyclin= drop in activity of mitotic Cdk= progression to G1
       • Chrom. movement
       • Spindle Checkpoint: b/w M and A--- checks for misaligned chroms. If this doesn't happen, aneuploidy results.
     • 4. Telophase: daughter cells return to interphase. mitotic spindle disassembles. nuclear env. reassembled. chroms disperse. Cytoplasm is partitioned in Cytokinesis.
       • Cytokinesis
         • Contractile ring Theory: a thin band of actin and myosin filament sgenerate force to cleave cell.
         • Filament Assembly happens when/where spindle pole gives signal
         • Bipolar myosin filaments= contraction
         • Cleavge Furrow: position where Ana mitotic spindle was. activates RhoA
         • Astral Microtubules cary signal for plane
         • cleavage plane and time cleavage occurs depends on mitotic spindle.
         • IN PLANTS
           • Formation of the cell plate, precursor to a new cell wall. Cells build a cell membrane and cell wall in the cell center. Cell plate begins with the appearance of the phragmoplast, which then proceeds laterally. Material for the cell wall is brought to the phragmoplast by Golgi vesicles.
   • Interphase (days to weeks+)
     • G1: b/w end of mitosis and beginning of DNA repl.
     • S Phase: DNA replication (length calculated by radioactively labeled nuclei of cells pulsed with [3H]thymidine)
     • G2: b/w end of S phase and beginning of mitosis

2. Cell Cycle Control

   • Checkpoints
     • arrests cells in cycle
       • DNA damge: Chk1 inhibits Cdc25
       • DNA damage: protein p21 inhibits G1 Cdk
     • Sensors: detect abnormal chrom. Transmitters: signal info. Effectors: inhibit cycle machinery
     • S-phase inhibited by p27 forming complex w/ CycA & Cdk2. Causes cell proliferation and organ growth
   • focus is start DNA repl. and mitosis
   • regulation of nucleus state
     • factors in cytoplasm of replicating cell stimulate DNA synth
     • factors in cytoplasm of cell in mitosis trigger chrom.cond.
   • G1-S and G2-M= positive control
   • Protein Kinases
     • MPF
     • Cyclin-dependent kinases (Cdks) in yeast cells
       • Examples: cdc2 and CDC28: responsible for passage thru control points
         • activated by cyclins
         • when active, Cdk phosphorylates specific proteins for specific transition: Start and G2-M
     • Cyclin Binding
       • binds to catalytic subunit of Cdk
       • type of cyclin depends on point of cycle
       • cyclin-cdk complex phosphorylates proteins
         • Cdc-activation kinase (CAK) ph. Threonine and tyrosine
           • doubly ph= inactivation
             • cdc25 removes one phosphate
               • other cyclin is
     • Cdk regulation
       • protein Sic1 (inhibitor) controls cycle progression
       • Proteolysis: SCF ubiquitin ligase promotes degradation of Sic1= entry to S phase
       • controlled by mv'mnt of cyclins b/w cytoplasm and nucleus
         • Cyclin B1: Ph. Serine of NES allowing it to enter nucleus
         • If cyclin blocked, no mitosis
     • Cdk1 is only Cdk rq'd to drive mammalian cell thru cycle
       • Knockout studies show Cdk1, CycB1, CycA1- if lost=lethal
         • pRB ph= expression of CycE, CycA, cdk1

3. Maturation Promoting Factor: is a protein kinase. when activated, triggers entry into M phase

   • MPF= a kinase + cyclin
     • cyclin increase (conc. is predicatable)= kinase activation
   • Experiments to support its role

4. how chromosomes move through Mitosis and Meiosis

   • Mitosis: cells are genetically identical. Basis for producing new cells. Maintains chrom. #. accompanied by Cytokinesis. haploid or diploid cells.
     • Anaphase= chrom movement
       • Dynein and Kinesin are at Spindle poles and Kinetochores. These are microtubule motors.
         • Depolymerization of microtubules= force
         • Features: keep poles apart in prometaphase. bring chroms to metaphase. elongate spindle in AnaB
       • in yeast: depolym pushes proteinto help move chrom.
   • Meiosis: cells w/ half genetic content. Basis for producingsexually reproducing organisms. chrom. # is halved and 4 daughter haploid cell sare formed
     • 2 divisions: DIV1: homologous chroms pair and then segegate. daughter cells receive full haploid set of chroms. DIV2: two chromatids are separated.
     • Occurs at Different Points in Eukarotes: gametic meiosis- gamete formation. zygotic meiosis- after fertilization in protists and fungi. sporic meiosis- indep. of gamete formation and fertilization
     • MALE GAMETES: In male vertebrates meiosis occurs just prior to the differentiation of the spermatozoa. Spermatogonia that are committed to undergo meiosis become primary spermatocytes. Then, two divisions of meiosis produces four relatively undifferentiated spermatids. Each spermatid undergoes a complex differentiation to become the highly specialized sperm cell (spermatozoon)
     • FEMALE GAMETES: In female vertebrates, oogonia become primary oocytes, which then enter a greatly extended meiotic prophase. Vertebrate eggs are typically fertilized at a stage before the completion of meiosis (usually at metaphase II). Meiosis is completed after fertilization, while the sperm resides in the egg cytoplasm.
     • DNA is replicated prior to meiosis
     • STAGES: Meiosis I
       • Prophase I consists of several stages: In leptotene chromosomal condensation starts. During zygotene homologous chromosomes pair. This process is called synapsis, and it is when homologues associate via the synaptonemal complex. The synaptonemal complex allows interacting chromatids to complete crossing-over. Synapsed chromosomes form a bivalent or tetrad. Association of the telomeres of meiotic chromosomes with the nuclear envelope. Homologous chromosomes are physically associated as part of a bivalent. In pachytene synapsis ends. During diplotene the synaptonemal complex disappears and homologous chromosomes start moving apart. Chiasmata are the remaining points of attachment between homologous chromosomes. Chiasmata occur where crossing over took place. The final stage of prophase I is diakinesis, when chromosomes are prepared for attachment to the spindle fibers. Diakinesis ends with the disappearance of the nucleolus and the disassembly of the nuclear envelope. Diakinesi
       • Metaphase I The two homologous chromosomes are aligned at the metaphase plate. Both chromatids of one chromosome face the same pole. Homologous chromosomes are held by one or several chiasmata. Absence of a chiasma can lead to abnormal segregation of chromosomes.
       • Anaphase I Stage when homologous chromosomes separate. Maternal and paternal chromosomes of each tetrad segregate into the two daughter cells independent of other chromosomes. Behavior of chromosomes during anaphase I corresponds to Mendel’s law of independent assortment.
       • Telophase I Produces less dramatic changes than telophase of mitosis. The nuclear envelope may or may not reform during this stage. The stage between the two divisions is called interkinesis. Cells during this stage have a haploid number of chromosomes. Cells have a diploid amount of DNA.
     • STAGES: Meiosis II is simpler than meiosis I. During metaphase II, chromosomes are aligned so that kinetochores of sister chromatids face opposite poles. Sister chromatids separate during anaphase II. Meiosis II produces cells haploid in both amount of DNA and chromosome number.
     • Genetic Recombination: Genetic Recombination During Meiosis Meiosis increases genetic variability by mixing maternal and paternal alleles between homologous chromosomes. Recombination occurs by the physical breakage of and ligation of individual DNA molecules. It occurs without the addition or loss of a single base pair. DNA repair enzymes fill gaps that develop during the exchange process. Prior to recombination, DNA strands are aligned by homology search, in which homologous DNA molecules associate with one another. Breaks are introduced into one strand of each duplex at corresponding sites. The gap is subsequently widened. The two duplexes are joined to each other by Holliday junctions (pairs of DNA crossovers).
     • Meotic Nondisjunction: Meiotic nondisjunction occurs when homologous chromosomes do not separate during meiosis I or sister chromatids do not separate during meiosis II. Nondisjunction leads to the formation of gametes and zygotes with abnormal number of chromosomes, or aneuploidy. The normal human chromosome complement is 46: 22 pairs of autosomes and one pair of sex chromosomes. An extra chromosome is referred to as a trisomy. Down syndrome is the result of trisomy of chromosome 21. All other autosomal trisomies are lethal. A missing chromosome is referred to as a monosomy. Monosomies, unless they involve a sex chromosome, invariably prove to be lethal during embryonic or fetal development.
       • The presence of an abnormal sex chromosome number is less disruptive to human development. A zygote with only one X chromosome leads to Turner syndrome, in which genitalia development is arrested. A male with an extra X chromosome develops Klinefelter syndrome, which leads to the presence of secondary female sex characteristics. There is no precise answer as to why meiosis I is more susceptible to nondisjunction than meiosis II. A possibility is that sister chromatid cohesion is not fully maintained over an extended period thus allowing homologous chromosomes to separate prematurely.

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