Novel genetic and epigenetic alterations in ... - Ous-research.no

Introductionamino acid change it is referred to as a silent mutation. Silent mutations can still have animpact on the correct transcription of genes if they occur close to an intron-exon boundary.If so, it may affect correct splicing of the exons and be referred to as a splicing mutation.The first two bases up- and downstream of an exon are called the acceptor and donor siteand consist of GT and AT, respectively. Alterations in any of these four bases will lead toexon skipping and a shorter protein[19]. Indels lead to frameshift mutations (except if theindel consists of a number of bases dividable by 3), which in most cases leads to a prematuretermination codon and a truncated protein.Figure 2. Cell cycle and timing of mutations. The different kinds of mutations occur at different stages inthe cell cycle. During G1, chemical compounds and UV-irradiation can cause DNA damage which needs to bedetected and repaired before the re-synthesis if mutations are to be prevented. Just before the G1/S-transision,the cell enters the restriction point, in which passing irreversibly commits the cell to undergo DNA re-synthesisand cell division. Only optimal conditions and minor DNA errors not detected by the repair machinery makesthe cell pass this point. If not, it will enter a quiescent G 0-state (not shown). During S-phase several DNArepairsystems work in order to obtain high DNA fidelity. Further, the same DNA damaging agents who causedamage in G1 are present in G2, which means that before cell division, the cell monitors the DNA quality andthe chromosome alignment before dividing.All bases have the same theoretical chance of being affected by mutations. Still, in humancancers we see a clear accumulation of mutation of specific bases in specific genes,14