MISMATCH REPAIR
Mismatch repair (MMR) is a
cellular mechanism that corrects errors that occur during DNA replication,
ensuring the accuracy of the genetic code. The primary targets of mismatch
repair are base-pair mismatches and insertion-deletion loops (IDLs) that can arise
due to DNA polymerase errors during replication. Here are the key steps
involved in mismatch repair:
1. Recognition of Mismatch:
- Recognition Proteins:
The process begins with the recognition of the mismatched base pairs by a
set of recognition proteins. In prokaryotes, the MutS protein is
responsible for recognizing mismatches, while in eukaryotes, the MutSα
and MutSβ
complexes fulfill this role.
2. Binding and Recruitment of
Repair Proteins:
- Recruitment of MutL:
Once a mismatch is recognized, MutS recruits MutL to form a MutS-MutL
complex. In eukaryotes, additional proteins like MutLα
and MutLβ
can be involved.
- Loading of Helicase:
The MutS-MutL complex helps to load a helicase, which unwinds the DNA in
the vicinity of the mismatch.
3. Excision of Mismatched
Segment:
- Exonuclease Action:
The unwound DNA region containing the mismatch is subject to exonuclease
activity, leading to the removal of the mismatched segment.
4. Resynthesis and Ligation:
- DNA Polymerase Action:
After the removal of the mismatched segment, a DNA polymerase synthesizes
a new DNA strand complementary to the template strand.
- Ligation:
The newly synthesized DNA strand is ligated to the existing DNA, sealing
the gap.
5. Final Verification and
Surveillance:
- Proofreading Mechanisms:
DNA polymerases involved in mismatch repair often have proofreading
capabilities, contributing to the accuracy of the repair.
- Surveillance Mechanisms:
Various surveillance mechanisms are in place to monitor the repaired DNA
for potential errors.
Key Features and
Significance:
- Correction of Replication Errors:
Mismatch repair corrects errors that occur during DNA replication,
preventing the propagation of mutations to subsequent generations.
- Correction of Small Insertion-Deletion
Loops: In addition to base-pair mismatches,
mismatch repair also addresses small insertion-deletion loops (IDLs) that
can occur during replication.
- Conservation:
Mismatch repair is highly conserved across evolution, highlighting its
fundamental role in preserving the fidelity of genetic information.
- Defects and Diseases:
Mutations in genes involved in mismatch repair are associated with a
condition known as Lynch syndrome, which predisposes individuals to
certain types of cancers, particularly colorectal cancer.
Mismatch repair is an
essential cellular process that contributes to the maintenance of genomic
stability. By correcting errors introduced during DNA replication, mismatch
repair helps prevent the accumulation of mutations and ensures the accurate
transmission of genetic information from one generation of cells to the next.
Key Elements:
- Recognition of Mismatch:
- Recognition Proteins (MutS/MutSα/MutSβ)
- Binding and Recruitment of Repair Proteins:
- MutS-MutL Complex Formation
- Loading of Helicase
- Excision of Mismatched Segment:
- Exonuclease Action
- Resynthesis and Ligation:
- DNA Polymerase Action
- Ligation
- Final Verification and Surveillance:
- Proofreading Mechanisms
- Surveillance Mechanisms
Key Features and Significance:
- Correction of Replication Errors
- Correction of Small IDLs
- Conservation Across Evolution
- Defects and Diseases (Lynch Syndrome)
Mismatch Repair Mind Map
| Steps | Enzymes | Significance |
|---|---|---|
| 1. Recognition of Mismatch | - MutS (prokaryotes and eukaryotes) | - Identifies base-pair mismatches and IDLs during replication. |
| 2. Binding and Recruitment | - MutL (prokaryotes and eukaryotes) | - Forms a MutS-MutL complex, facilitating further steps. |
| - Helicase (prokaryotes and eukaryotes) | - Unwinds DNA in the vicinity of the mismatch. | |
| 3. Excision of Mismatched Segment | - Exonuclease (prokaryotes and eukaryotes) | - Removes the mismatched segment. |
| 4. Resynthesis and Ligation | - DNA Polymerase (prokaryotes and eukaryotes) | - Synthesizes a new DNA strand. |
| - Ligase (prokaryotes and eukaryotes) | - Seals the gap in the DNA strand. | |
| 5. Final Verification and Surveillance | - Proofreading Mechanisms | - Ensures accuracy of repair. |
| - Surveillance Mechanisms | - Monitors repaired DNA for potential errors. |