Rate of spontaneous mutation at any given site on chromosomal ranges from 10-6 to 10-11 per round of DNA replication with some sites being hotspot Mutation-prone sequence in human genome are repeats of simple di, tri or tetranucleotide sequences, known as dna microsatellites(微卫星DNA These sequences(1)are important in human genetics and disease, (2) hard to be copied accurately and highly polymorphic in the population
Rate of spontaneous mutation at any given site on chromosomal ranges from 10-6 to 10-11 per round of DNA replication, with some sites being “hotspot” . Mutation-prone sequence in human genome are repeats of simple di-, trior tetranucleotide sequences, known as DNA microsatellites (微卫星DNA). These sequences (1) are important in human genetics and disease, (2) hard to be copied accurately and highly polymorphic in the population
Some replication errors escape proofreading The 3-5 exonuclease activity of replisome only improves the fidelity of dna replication by a factor of 100-fold g The misincorporated nucleotide needs to be detected and replaced, otherwise it will cause mutation
Some replication errors escape proofreading The 3’-5’ exonuclease activity of replisome only improves the fidelity of DNA replication by a factor of 100-fold. The misincorporated nucleotide needs to be detected and replaced, otherwise it will cause mutation. Replication errors and replication
repair second round replication T CG T first round replication(mis incorporation) GCTCA G Fiqure 9-2 Generation of Mutation
Figure 9-2 Generation of Mutation
Mismatch repair removes errors that escape proofreading Increase the accuracy of dNA synthesis for 2-3 orders of G magnitudes 3. Two challenges:(1)rapidly find the mismatches/mispairs,(2) Accurately correct the mismatch Talking about the story of E, coli repair system
Mismatch repair removes errors that escape proofreading Increase the accuracy of DNA synthesis for 2-3 orders of magnitudes. Two challenges: (1)rapidly find the mismatches/mispairs, (2) Accurately correct the mismatch Replication errors and replication Talking about the story of E. coli repair system
Muts scans the DNA, recognizing the mismatch from the distortion they cause in the dna backbone Muts embraces the mismatch-containing DNA inducing a pronounced kink in the DNA and a conformational change in Muts itself Muts 3 3'Q 5 ATP
MutS scans the DNA, recognizing the mismatch from the distortion they cause in the DNA backbone MutS embraces the mismatch-containing DNA, inducing a pronounced kink in the DNA and a conformational change in MutS itself