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MolBio (Subject) / Lecture 7 (Lesson)
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- Parts of the cytoskeleton microtubules microfilaments (=actin filaments) intermediate filaments
- Function of the cytoskeleton maintain cell shape position organelles resist deformation transport intracellular cargo
- Microtubules composed of protein tubulin Diameter: 25nm α-tublin + β-tubulin = protofilament 1 microtuble = 10-15 protofilaments can rapidly grow/shrink (polymerization/depolymerization)
- Microfilaments (=actin Filaments) composed of contractile protein actin diameter: 8nm prevalent (häufig) in muscular cells
- Intermediate filaments different protein subunits diameter: 10nm associated with specific cell types -neurofilaments > neuron -desmin > muscle cells -keratin > epithelial cells
- Motor Proteins use energy from ATP-Hydrolysis 3 types: -Kinesin: towards cell membrane -Dynein: towards nucleus -Myosin: interacts with actin for muscle contraction (+involved in cytokinesis, endo- and exocytosis)
- Cell cycle (Phases) G1 - (G0) - S - G2 - M
- Mitosis (in General) somatic cell division to get two genetically identical daughter cells Mitosis = nuclear division (karyokinesis) only for tissue growth, regeneration and asexual reproduction 5 Phases: -Pro- -Prometa- -Meta- -Ana- -Telo-
- Cytokinesis (second step of M-Phase) division of cytoplasm and organelles
- Regulation of mitosis CDK ensure cell cycle progression (Cyclin-dependent kinases) Kinase = adds phosphate group CDK get active when cycline is present cycline concentration fluctuates, CKD concentration is stable [In M-Phase Cyclin B for CDK1]
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- PLK and Aurora Kinases Polo-like kinases (PLK) + Aurora kinases control phosphorylation major regulators of: -centrosome function -spindle assembly -chromosome segregation -cytokinesis
- Prophase (8) CCCNNHHM Condensins coil chromosoms in compact form H1 histone phosphorylation and attachment of condensins is mediated by CDK1 H3 histone phosphorylation is mediated bei Aurora B kinase Cohesins forms ring that hold sister chromatids together nuclear membrane breaks down (is packed into small vesicles) nucleolus disintegrates beginning of formation of mitotic spindle Centrosome moves to the cells poles (mediated by PLKs and Aurora A kinase
- Centrosome minus end of microtubules is anchored at microtubule organizing center (MTOC) [Polymerization of microtubules happens at the "+" end) is made up of two centrioles duplicates during S-Phase
- Centrioles paired cylindrical organelles constructed of microtubules produce mitotic spindle fibres
- Prometaphase (2) Spindle fibres bind to kinetochor chromosomes migrate to metaphase plate
- Metaphase (3+2) lined up chromosomes mitotic spindle checkpoint can be activated (in case of mitotic spindle assembly error) mediated by: -Anaphase-promoting complex/cyclosome (APC/C) -cyclin A & B
- Anaphase(2) sister chromatid separation, breakdown of cohesins seperated sister chromatids = daughter chromosoms
- Microtubules in Anaphase Astral microtubules (Microtubules which go to the cell membrane; no connection to the other centromere or with chromosomes) -ensure positioning and orientation Kinetochor microtubules (Microtubules which attach to the chromosomes) -attach to the kinetochor, pull chromatids Interpolar microtubules (microtubules which go from one centromere to the other)
- Telophase (4+1) chromosomes arrive at cell poles mitotic spindle disassembles vesicles (with nuclear membrane) assemble around the chromosomes Phosphatases dephosphorylate lamins -leads to formation of new nuclear membrane
- Cytokinesis split into two identical daugther cells start signal = dephosphorylation of CDKs target Proteins cleavage furrow is formed by contractile ring of actin + myosin
- Biological role of mitosis Growth (of the organism) Repair Replaicement (-Verjüngung) Asexual reproduction
- Meiosis (in General) diploid cells -> haploid gametes (achieved by two rounds of division with one round of replication unique to germ cells
- Prophase I [LZPDD] Leptotene: Condensation of chromosomes Zygotene: homologous chromosomes begin to form synapsis; hold together by synaptonemal complex Pachytene: bivalent;crossing over Diplotene: synaptonemal complex breaks down, but chromosomes remain attached by chiasmata Diakinesis: only the terminal chiasmata connects the two chromosomes
- Crossing over = "exchange of genetic material between non sister chromatids during Meiosis" generates genetic variability ensured by homologous recombination
- Homologous recombination DNA gets broken, fragments get newly re-joined recombination complex is responsible for homologous reparation after DSB DSB => Proteins with topoisomerase activity
- Metaphase I (3) nuclear membrane disappears spindle forms bivalent -> equatorial plane
- Anaphase I disjunction happens random segregation (distribution of chromosomes) 223 combinations possible
- Telophase I (1) two haploid sets at poles of the cell
- Cytokinesis (Meiosis) Division in two haploid daughter cells enters meiotic interpahse -when compared to mitosis is this phase brief -Interkinesis + Meiosis II begins
- Meiosis II similar to Mitosis, but cells are haploid no DNA-replication
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- Human Pathology: Down-Syndrome 95% caused by non-disjunction -rest is caused by chromosome translocation 90-95% the extra-chromosome comes from the mother Mosaicism can sometimes be found (2-4%)
- Mosaicism Somatic mosaicism: -two genetically distinct population of cells within an individual Germline mosaicism: -genetically distinct groups within germ line tissue
- Mitochondrial Mosaicism often heterogenous, because of higher mutation rate for mitochondria mitochondrial segregation occurs randomly, cells will recieve similar, but not identical mitochondrial DNA populations
- Tumorgenesis tumor cells are characterized by genomic instability (chromosome breaks, aneuploidy) aneuploidy can contribute to tomorgenesis -extra copies of oncogenes -deleting tumor suppressor genes
- UPD (uniparental disomy) two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other parent dysregulation of imprinted genes can occur because of a trisomy (+Rescue mechanism)