mismatch repair
Summary
Mismatch repair is a post-replication pathway that removes wrongly paired but chemically normal bases from the newly made DNA strand and refills the gap. The testable point is strand choice: bacteria mark the parent strand by methylation, while eukaryotes are thought to use nicks or ends in the new strand.
Detail
Meaning: Mismatch repair fixes wrongly paired bases, such as A opposite C, that remain after replication because polymerase proofreading missed them. A protein complex (MutS in E. coli) detects the distortion, a stretch of the new strand containing the error is cut out, DNA polymerase refills the gap, and DNA ligase seals the nick. The cell must target the new strand, because the template holds the correct sequence. In E. coli the parent strand is recognized by its methylation, while the new strand is briefly unmethylated. In eukaryotes, nicks or ends in the new strand are thought to mark it.
On the MCAT: Passages ask you to place repair systems by timing and by what they fix. Proofreading acts during synthesis, and mismatch repair acts just after it. Cells lacking mismatch repair show a higher spontaneous mutation rate. If the template strand were cut instead of the new strand, the error would become a permanent mutation.
Common confusion: Mismatch repair is not the same as excision repair of damaged DNA. Base excision repair and nucleotide excision repair remove chemically altered bases or bulky lesions such as UV-induced thymine dimers. Mismatch repair handles normal bases that are paired incorrectly.
Sources
- Lehninger Principles of Biochemistry
- Molecular Biology of the Cell
- Biochemistry (Berg, Tymoczko, Stryer)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.