Explain your understanding of mismatch repair How does misma

Explain your understanding of mismatch repair. How does mismatch repair occur in mammalian cells where there is no methylation of DNA similar to what is observed in bacteria?

Solution

mismatch defect occurs during DNA replication and recombination, as well as repairing some forms of DNA damage. For instance cytosine (instead of thymine) could be incorporated oppsosite to adenine. Mismatch repairs corrects a single mismatch base pair. For example C to A, instead of T to A. In gram negative bacteria, the template strand of the DNA exists in a methylated form, while the newly synthesized strand is not methylated. This difference allows the recognition of the new strand by mismatch repair machinery. The enzyme GATC endonuclease cuts the strand at an adjecent methylated GATC sequence. This is followed by an exonuclease digestion of the defective strand and thus its removal. A new DNA is synthesized to replace the damaged one with the help of DNA polymerase and DNA ligase. However, in other prokaryotes and eukaryotes, the exact mechanism is not clear. It is suspected that, in eukaryotes, newly synthesized lagging-strand DNA transiently contains nicks (before being sealed by DNA ligase) and provides a signal that directs mismatch proofreading systems to the appropriate strand. This implies that these nicks must be present in the leading strand, and evidence for this has recently been found. Recent work has shown that nicks are sites for RFC-dependent loading of the replication sliding clamp PCNA, in an orientation-specific manner, such that one face of the donut-shape protein is juxtaposed toward the 3\'-OH end at the nick. Oriented PCNA then directs the action of the MutLalpha endonuclease to one strand in the presence of a mismatch and MutSalpha or MutSbeta.