5

Onko (Fach) / 4. Geley (Lektion)

Diese Lektion wurde von bergs85 erstellt.

Lektion lernen

Diese Lektion ist leider nicht zum lernen freigegeben.

zurück  |  weiter 1 / 1

• Causes of genetic instability and its role in cancerogenesis DNA or chromosomal (Aneuplidy) mutations cause genetic instability. Sporadic replication or repair errors. Examples: DNA damage response defect (p53) loss of differenciation signals (loss of APC) Hyperproliferation (RAS) Massive proliferation+mistakes p53 loss (Vermutlich main reason) Microsatellite instability, caused by impaired missmatch repair Role in cancerogenesis: Selection of the fittest is enhanced. Facilitates Tumorigenesis: Aneuploidy-tolerating mutations; Genetic heterogeneity; Genomic instability Inhibits Tumorigenesis: Stress response; Impaired Fitness Genetic instability Pathways: BER and NER; MMR; Telomere maintenance, DSBR, DNA replication, Chromosome segregation
• Cell cycle regulation and cell cycle checkpoints G1-CdK → cylcin D + CdK4,6 (regulated by RB) Inhibitors: INK4A family proteins G1/S -CdK --> cylcin E + CdK2 (regulated by P53) Inhibitors CIP/KIP proteins S-CdK → cyclin A + CdK2,1 M-CdK→  cylcin B + CdK1  
• DNA damage and DNA damage responses Damage: Endogenous: Depurinierung, Deaminierung (Cytosine), Oxidation, Methylierung. Repair: Base excision repair (BER) Transcription coupled repair (TCR); work together with RNApol Non homologuous end joining (NHEJ): Double strand break repair. Als PR markiert:Quality control during cell cycle Cells need to make sure that: No damage is fixed during replicationReplicates DNA with highest fidelityDoes not divide if chromosomes are brokenDoes not divivde if DNA is not completely replicated
• Regulation of mitosis and the spindle assembly checkpoint Spindle assembly checkpoint: Prevents anaphase until all the the chromosomes are stable attached to the spindles. the SAC (spindle assambly checkpoint) does not monitor spindle assembly per se but rather the status of kinetochore–microtubule attachment. In the presence of unattached kinetochores the SAC is ‘on’ and anaphase is inhibited.The SAC only becomes satisfied when all kinetochores are stably bound to microtubules; inhibition of anaphase is then alleviated and the cell cycle can continue. (sciencedirect) APC/C (anaphase promoting complex) regulates anaphase and exit from mitosis and resets the DNA replication cycle.As long as kineteochore is not attached it blocks ubiquitin ligase by inducing signals, when this signal stops APC/C is activated and generate an anaphase-wait signal. Removal of cohesion ring is a critical point, cleaved through separases
• Tumor evolution: inter- and intratumor heterogeneity; causes and consequences Tumors are genetically heterogeneousin general the show a branched revolution high mutation rate many subclones in one tumor early cancers show more genetic diversity than metastatic cancers heterogenity - difficult to treat with cehmo, after chemo more homogenous cancerogenesis requires multiple (epi) genetic chances to overcome barriers that limit proliferation

zurück  |  weiter 1 / 1