DNA Polymerase slippage

During replication, the slipping of DNA polymerase III from the DNA template strand at the repeat region and the subsequent reattachment at a more distant site. Polymerase slippage can cause the newly created DNA strand to contain an expanded section of DNA. Slipped strand mispairing (SSM), (also known as replication slippage), is a mutation process which occurs during DNA replication. It involves denaturation and displacement of the DNA strands, resulting in mispairing of the complementary bases. Slipped strand mispairing is one explanation for the origin and evolution of repetitive DNA sequences. It is a form of mutation that leads to either a trinucleotide or dinucleotide expansion, or sometimes contraction, during DNA replication. A slippage event normally occurs when a sequence of repetitive nucleotides (tandem repeats) are found at the site of replication. Tandem repeats are unstable regions of the genome where frequent insertions and deletions of nucleotides can take place, resulting in genome rearrangements. DNA polymerase, the main enzyme to catalyze the polymerization of free deoxyribonucleotides into a newly forming DNA strand, plays a significant role in the occurrence of this mutation. When DNA polymerase encounters a direct repeat, it can undergo a replication slippage. Strand slippage may also occur during the DNA synthesis step of DNA repair processes. Within DNA trinucleotide repeat sequences, the repair of DNA damage by the processes of homologous recombination, non-homologous end joining, DNA mismatch repair or base excision repair may involve strand slippage mispairing leading to trinucleotide repeat expansion when the repair is completed. Stages Slippage occurs through five main stages: - In the first step, DNA polymerase encounters the direct repeat during the replication process. - The polymerase complex suspends replication and is temporarily released from the template strand. - The newly synthesized strand then detaches from the template strand and pairs with another direct repeat upstream. - DNA polymerase reassembles its position on the template strand and resumes normal replication, but during the course of reassembling, the polymerase complex backtracks and repeats the insertion of deoxyribonucleotides that were previously added. This results in some repeats found in the template strand being replicated twice into the daughter strand. This expands the replication region with newly inserted nucleotides. The template and the daughter strand can no longer pair correctly. - Nucleotide excision repair proteins are mobilized to this area where one likely outcome is the expansion of nucleotides in the template strand while the other is the absence of nucleotides. - — Although trinucleotide contraction is possible, trinucleotide expansion occurs more frequently. Slipped strand mispairing has also been shown to function as a phase variation mechanism in certain bacteria. #NikolaysGeneticsLessons #TripletRepeatExpansion #Mutation #HuntingtonsDisease #FragileXSyndrome #bmhLearningDNA #nonCanonicalDNAStructure #Slipped #DNAStructureSlippedDNA #slippedDna #DNAPolymeraseSlippage #Dna #DNAStructure #NucleicAcidStructureLiteratureSubject #structureOfDNA #dnaChemicalStructure #dnaStructureAndReplication #dnaStructureAndFunction #dnaAndRnaStructure #biochemistry #DNARepair #PointMutation #SilentMutation