Proof reading and Mismatch repair are crucial processes in DNA replication, their existence reduces the likelihood of a mutation occurring by a significant amount. In fact, proofreading reduces the likelihood of errors occurring to approximately one in every ten million nucleotides (Pierce, 2012-pp354). This essay will emphasise the importance of proofreading during, and mismatch repair post DNA replication and explore its significance in the mechanisms that drive Lynch syndrome.
In eukaryotes 3 DNA polymerases are used for Elongation; DNA polymerase α, DNA polymerase δ and DNA polymerase ε. DNA polymerase α acts as a primase and forms the RNA primer at the 3’ end of the template strand because DNA nucleotides cannot be added de novo- there …show more content…
These are highly studied in E. coli, but the exact mechanism in Eukaryotes such as humans is still being explored. The mechanism is highly conserved across all kingdoms and thus researches believe that in humans a hMutSα complex activated by the binding of ATP- (when ADP is bound the protein complex is in its resting state) this will cause a conformational change, activating the complex and causing it to move along the DNA strand signalling other proteins and complexes involved in MMR. It is proposed that the hMutLα complex will coordinate the proteins involved in MMR such as endonucleases and DNA polymerases (δ and ε) (Nyström-Lahti, Peltomäki 2006). The endonuclease will hydrolyze the phosphodiester bond, cleaving the DNA close to the site of the mismatched base (Berg, Stryer, Tymoczko, 2007). The proteins involved in MMR must be able to differentiate between the two strands; the correct template strand, and the mutant new strand. In E.coli the presence of methyl groups on the template strand allows recognition, so that the MMR complex can nick the strand at the methylated site and degrade the DNA between this and the incorrectly inserted bases (Pierce,2012). But how does the MMR machinery decipher which strand obtains the mismatched
In eukaryotes 3 DNA polymerases are used for Elongation; DNA polymerase α, DNA polymerase δ and DNA polymerase ε. DNA polymerase α acts as a primase and forms the RNA primer at the 3’ end of the template strand because DNA nucleotides cannot be added de novo- there …show more content…
These are highly studied in E. coli, but the exact mechanism in Eukaryotes such as humans is still being explored. The mechanism is highly conserved across all kingdoms and thus researches believe that in humans a hMutSα complex activated by the binding of ATP- (when ADP is bound the protein complex is in its resting state) this will cause a conformational change, activating the complex and causing it to move along the DNA strand signalling other proteins and complexes involved in MMR. It is proposed that the hMutLα complex will coordinate the proteins involved in MMR such as endonucleases and DNA polymerases (δ and ε) (Nyström-Lahti, Peltomäki 2006). The endonuclease will hydrolyze the phosphodiester bond, cleaving the DNA close to the site of the mismatched base (Berg, Stryer, Tymoczko, 2007). The proteins involved in MMR must be able to differentiate between the two strands; the correct template strand, and the mutant new strand. In E.coli the presence of methyl groups on the template strand allows recognition, so that the MMR complex can nick the strand at the methylated site and degrade the DNA between this and the incorrectly inserted bases (Pierce,2012). But how does the MMR machinery decipher which strand obtains the mismatched