1. ΤΕΛΟΜΕΡΗ

2. Figure 5-43. Telomere replication
Figure Telomere replication. Shown here are the reactions involved in synthesizing the repeating G-rich sequences that form the ends of the chromosomes (telomeres) of diverse eucaryotic organisms. The 3 end of the parental DNA strand is extended by RNA-templated DNA synthesis; this allows the incomplete daughter DNA strand that is paired with it to be extended in its 5 direction. This incomplete, lagging strand is presumed to be completed by DNA polymerase a, which carries a DNA primase as one of its subunits (see Figure 5-28). The telomere sequence illustrated is that of the ciliate Tetrahymena, in which these reactions were first discovered. The telomere repeats are GGGTTG in the ciliate Tetrahymena, GGGTTA in humans, and G1 3A in the yeast S. cerevisiae. 2

3. Figure How the replication of damaged DNA can lead to chromosome abnormalities, gene amplification and gene loss. The diagram shows one of several possible mechanisms. The process begins with accidental DNA damage in a cell that lacks functional p53 protein. Instead of halting at the p53-dependent checkpoint in the division cycle, where a normal cell with damaged DNA would pause until the damage was repaired, the p53-defective cell enters S phase, with the consequences shown. Once a chromosome carrying a duplication and lacking a telomere has been generated, repeated rounds of replication, chromatid fusion, and unequal breakage (the so-called breakage-fusion-bridge cycle) can increase the number of copies of the duplicated region still further. Selection in favor of cells with increased numbers of copies of a gene in the affected chromosomal region will thus lead to mutants in which the gene is amplified to a high copy number. The multiple copies may eventually become visible as a homogeneously staining region in the chromosome, or they may either through a recombination event or through unrepaired DNA strand breakage become excised from their original locus and so appear as independent double minute chromosomes (see Figure 23-28). The chromosomal disorder can also lead to loss of genes, with selection in favor of cells that have lost tumor suppressors. 3

5. ΑΥΞΗΤΙΚΟΙ ΠΑΡΑΓΟΝΤΕΣ

7. G-proteins

8. Signaling through G-proteins

10. Activation of IP3 pathway

23. Cdk2, Cdk4
Cyclin D, E
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Αυξητικούς Παράγοντες

24. (Akt)

26. Bad, Bax = proapoptotic
Bcl-2, Bcl-xL =antiapoptotic