PPT 4 Flashcards
Best defense against cancer
DNA stability
Tissues minimize accumulations of mutations by
- Small stem cell compartment
- Snelle regeneration of tissues
- Symmetic & assymetic stem cel division
Transit-amplifying cell (TACs)
2nd daughter cell of stem cell
undifferentiated population in transition between stem cells and differentiated cells
symmetic division
Van 1 stam cell -> 2 stam cellen
- growth of organ, increases number of stem cells
Assymmetric divison
van 1 stam cell -> 1 stam cel + 1 transit-amplifying cell
- maintenance of organ size, constant number of stem cells
Targets for oncogenic transormations
- Stem cells (permanently present in tissues)
- Transit-amplifying cells (hoger aantal dan SC, actively dividing
Protective mechanisms
- Apoptosis
- Drug pumps
- Assymmetic DNA replication
> (proofreading)
Barriers for mutagenesis
- DNA replication
- Mismatch repair (MMR)
- Double-strand break (DSB) repair
Source mutagenesis
- Endogenous (Depurination, deprimidination, deamintion, Oxidation by ROS, reactive oxygen species, base mispairing)
- Exogenous (Ionizing radiation, UV, alkylating agents, cellular processes, alcohol)
Cell protects DNA by
- Physical shielding (melanine)
- Reactive oxygen species (ROS) scavengers (Vitamine C, bilirubin, urate) react with ROS
- Enzymes (Glutamthionine S-transferase (GSTs) inactivate electrophilic compounds by linking them with glutathionine
DNA repair proteins
- Base-excision repair (BER)
- Nucleotide excision repair (NER)
(defects cause cancer)
Double strand break repair
- Homologous recombination (HR)
Active in S en G2 phase - Non-homologous end joining (NHEJ)
mostly active in G2
Changes in chromosome structure
- Deletions
- Amplifications
- Translocations
> can lead to loss of heterogeneity (LOH) = loss of 1/1+ alleles of a specific gene
Chromosome Aberrations
changes in structure or number of chromsomes
Chromothripsis
localized, massive chromosome fragmentation, followed by multiple rejoining between resulting fragments.
