Note: Mechanisms of DNA double-strand break repair and their potential to induce chromosomal aberrations
Note: Mechanisms of DNA double-strand break repair and their potential to induce chromosomal aberrations_2000
Theory of cancer formation
Breakage and reunion theory
Exchange theory
Molecular theory
Initial lesion -- chemical and physical-DNA damaging agents
Artificially induced DSB
IR
Endonuclease
Cellular (spontaneous) sources of DSB
Can occur in any stage of cell cycle
Briefly summarize the main causes of spontaneous DSB
Topoisomerases
Topo-I -- generates SSB
Topo-II -- generate DSB
Replication
Prevalent source of DSB -- DNA replication
Cell estimates to suffer ~ 10 DSB/cell cycle (estimate from spontaneous sister chromatid exchange)
Meiosis
V(D)J recombination
Other recombinant process
Transposable elements
Fragile sites
Extended micro- and minisatellite sequences -- potential source of DSB in mammalian genome
At this time of writing (2000) -- the instability of this fragile site is not well-understood
DSB as a results of excision repair
Considering on the site which SSB could be occurred
20,000 oxidative lesion -- daily in DNA
10,000 apurinic/apyrimidinic sites/cell/day
Deamination of cytosine to uracil and 5-methylcytosine to thymine -- 100/cell/day
If SSB located close together -- <10 bp apart on opposite strands -- it would cause DSB during the SSB repair
Mechanisms of DSB repair -- mostly learning through rare diseases
Human chromosome instability syndromes
Nijmegen breakage syndrome
Fanconi anemia
Bloom syndrome
Werner syndrome
Ataxia telangiectasia
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