DNA Repair: Difference between revisions

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==DNA Mismatch Repair by MutH==
==DNA Mismatch Repair by MutH==


DNA Mismatch Repair (MMR) occurs when a mismatch of DNA bases occurs during DNA replication that is not corrected by the polymerases. This mismatch can be at a single nucleotide or an insertion or deletion of up to 4 bases. In ''E. coli'', MutS, MutL, MutH, DNA helicase II (MutU/UvrD), four exonucleases (ExoI, ExoVII, ExoX, and RecJ), single-stranded DNA binding protein (SSB), DNA polymerase III holoenzyme, and DNA ligase are all required for mismatch repair <ref>PMID:18157157</ref>.
DNA Mismatch Repair (MMR) occurs when a mismatch of DNA bases occurs during DNA replication that is not corrected by the polymerases. This mismatch can be at a single nucleotide or an insertion or deletion of up to 4 bases. In ''E. coli'', <scene name='41/417575/Muts_mutl/1'>MutS, MutL</scene>, MutH, DNA helicase II (MutU/UvrD), four exonucleases (ExoI, ExoVII, ExoX, and RecJ), single-stranded DNA binding protein (SSB), DNA polymerase III holoenzyme, and DNA ligase are all required for mismatch repair <ref>PMID:18157157</ref>.


An integral protein in MMR is MutH. MutH is an endonuclease, which means it is an enzyme that can digest DNA in the middle of the sequence. However, it is a weak endonuclease so it will only cause a single-stranded nick upstream or downstream of the damaged daughter strand DNA and not the correct parent strand. This allows it to be re-replicated as the correct sequence by DNA polymerase. Homodimers of MutS and MutL bind the mismatched DNA and create a loop that MutH can bind to. Therefore, MutS and MutL are necessary to recruit MutH to nick the DNA. In order to maintain the correct DNA sequence and repair the damaged portion without mutations, MutH must be able to differentiate the incorrect daughter strand from the correct parent strand. In bacteria, the freshly replicated DNA is hemimethylated, meaning that the parent strand is methylated and the daughter strand has not yet been methylated by methyltransferases. MutH then nicks the phosphodiester bond 5' of a GATC palindrome on the umethylated daughter strand. The GATC palindrome can be upstream or downstream of the damaged DNA site by up to 1000 nucleotides. This allows the damaged strand to be destroyed by exonucleases and re-replicated by DNA polymerase as the correct sequence.  
An integral protein in MMR is <scene name='92/925551/2x_muth/1'>MutH</scene>. MutH is an endonuclease, which means it is an enzyme that can digest DNA in the middle of the sequence. However, it is a weak endonuclease so it will only cause a single-stranded nick upstream or downstream of the damaged daughter strand DNA and not the correct parent strand. This allows it to be re-replicated as the correct sequence by DNA polymerase. Homodimers of MutS and MutL bind the mismatched DNA and create a loop that MutH can bind to. Therefore, MutS and MutL are necessary to recruit MutH to nick the DNA. In order to maintain the correct DNA sequence and repair the damaged portion without mutations, MutH must be able to differentiate the incorrect daughter strand from the correct parent strand. In bacteria, the freshly replicated DNA is hemimethylated, meaning that the parent strand is methylated and the daughter strand has not yet been methylated by methyltransferases. MutH then nicks the phosphodiester bond 5' of a GATC palindrome on the umethylated daughter strand. The GATC palindrome can be upstream or downstream of the damaged DNA site by up to 1000 nucleotides. This allows the damaged strand to be destroyed by exonucleases and re-replicated by DNA polymerase as the correct sequence.