ΚΑΡΚΙΝΟΓΟΝΟΙ ΠΑΡΑΓΟΝΤΕΣ Χημικά Ακτινοβολία Ιοί

ΑΜΕΣΗ ΜΕΤΑΒΟΛΗ ΧΗΜΙΚΗΣ ΔΟΜΗΣ ΒΑΣΕΩΝ DNA ΛΑΝΘΑΣΜΕΝΟ ΖΕΥΓΑΡΩΜΑ ΒΑΣΕΩΝ

ΕΜΜΕΣΗ ΜΕΤΑΒΟΛΗ ΧΗΜΙΚΗΣ ΔΟΜΗΣ ΒΑΣΕΩΝ DNA ΕΝΕΡΓΟΠΟΙΗΣΗ ΑΠΟ ΕΝΖΥΜΑ ΤΟΥ ΟΡΓΑΝΙΣΜΟΥ

ΕΠΙΔΡΑΣΗ ΙΟΝΙΖΟΥΣΑΣ ΑΚΤΙΝΟΒΟΛΙΑΣ

ΕΠΙΔΡΑΣΗ ΥΠΕΡΙΩΔΟΥΣ ΑΚΤΙΝΟΒΟΛΙΑΣ

ΑΥΘΟΡΜΗΤΕΣ ΜΕΤΑΒΟΛΕΣ ΒΑΣΕΩΝ DNA

ΤΥΠΟΙ ΜΕΤΑΒΟΛΩΝ ΒΑΣΕΩΝ DNA

ΕΝΖΥΜΙΚΑ ΣΥΣΤΗΜΑΤΑ ΕΠΙΔΙΟΡΘΩΣΗΣ DNA

Inherited Syndromes with Defects in DNA Repair NAME PHENOTYPE ENZYME OR PROCESS AFFECTED MSH2, 3, 6, MLH1, PMS2 colon cancer mismatch repair Xeroderma pigmentosum (XP) groups A  G skin cancer, cellular UV sensitivity, neurological abnormalities nucleotide excision-repair XP variant cellular UV sensitivity translesion synthesis by DNA polymerase d Ataxia  telangiectasia (AT) leukemia, lymphoma, cellular g-ray sensitivity, genome instability ATM protein, a protein kinase activated by double-strand breaks BRCA-2 breast and ovarian cancer repair by homologous recombination Werner syndrome premature aging, cancer at several sites, genome instability accessory 3 -exonuclease and DNA helicase Bloom syndrome cancer at several sites, stunted growth, genome instability accessory DNA helicase for replication Fanconi anemia groups A  G congenital abnormalities, leukemia, genome instability DNA interstrand cross-link repair 46 BR patient hypersensitivity to DNA-damaging agents, genome instability DNA ligase I

ΟΓΚΟΓΟΝΟΙ ΙΟΙ Ιοί με δίκλωνο DNA

ONCOGENIC VIRUS

Figure 23-34. How certain papillomaviruses are thought to give rise to cancer of the uterine cervix. Papillomaviruses have double-stranded circular DNA chromosomes of about 8000 nucleotide pairs. In a wart or other benign infection these chromosomes are stably maintained in the basal cells of the epithelium as plasmids whose replication is regulated so as to keep step with the chromosomes of the host (left). Rare accidents can cause the integration of a fragment of such a plasmid into a chromosome of the host, altering the environment of the viral genes. This (or possibly some other cause) disrupts the control of viral gene expression. The unregulated production of viral replication proteins interferes with the control of cell division, thereby helping to generate a cancer (right).

Figure 23-35. Activation of cell proliferation by a DNA tumor virus Figure 23-35. Activation of cell proliferation by a DNA tumor virus. Papillomavirus uses two viral proteins, E6 and E7, to sequester the host cell's p53 and Rb respectively. The SV40 virus (a related virus that infects monkeys) uses a single dual-purpose protein called large T antigen, for the same purpose. The E6 protein binding leads to ubiquitylation of its p53 partner, inducing p53 proteolysis (not shown).

ΟΓΚΟΓΟΝΟΙ ΙΟΙ 2. Ρετροιοί

ΤΕΛΟΜΕΡΗ

Figure 5-43. Telomere replication Figure 5-43. 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.

Figure 5-43. Telomere replication Figure 5-43. 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.

Figure 23-33. 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.