The primary DNA repair system responsible for detecting and repairing base pairs that are not bonded correctly is DNA mismatch repair (MMR).
Understanding DNA Mismatch Repair (MMR)
DNA mismatch repair (MMR) is a highly conserved and critical cellular pathway that safeguards the integrity of the genome. Its main function is to correct non-Watson-Crick base pairs—those incorrect pairings of DNA bases that deviate from the standard adenine (A) with thymine (T) and guanine (G) with cytosine (C) pairings.
These errors can arise from several sources:
- Replication errors: This is the most common source, where DNA polymerase occasionally inserts an incorrect base during DNA synthesis.
- Recombination intermediates: Errors can occur during the process of genetic recombination.
- Chemical damage: Certain forms of chemical damage to DNA can also lead to mispaired bases.
How MMR Identifies and Corrects Errors
The MMR system is remarkably efficient at identifying and correcting these mispaired bases. A key challenge for MMR is distinguishing the correct parental strand from the newly synthesized daughter strand containing the error. This process is known as strand discrimination.
While the damaged bases themselves do not identify the error-containing strand, the MMR system utilizes other molecular cues to direct the repair machinery. For example, in many organisms, the system recognizes the difference between the methylated parental strand and the unmethylated nascent strand. Once the error is located and the incorrect strand identified, the MMR process generally involves:
- Mismatch Recognition: Specialized proteins, such as MutS and MutL homologs, detect the presence of the mispaired bases or small insertion/deletion loops.
- Strand Discrimination: The system identifies which of the two DNA strands contains the error. This is crucial to ensure the correct base is restored.
- Excision: A segment of the error-containing strand, including the mismatch, is removed.
- Resynthesis: DNA polymerase synthesizes a new, correct segment of DNA, using the intact parental strand as a template.
- Ligation: DNA ligase seals the nicks in the DNA backbone, completing the repair.
Why MMR is Essential
The integrity of our genetic material is paramount for proper cellular function and organismal health. MMR plays a vital role in:
- Maintaining Genome Stability: By correcting replication errors, MMR significantly reduces the mutation rate, preventing the accumulation of harmful mutations.
- Preventing Disease: Deficiencies in the MMR system are strongly linked to an increased risk of various cancers, particularly hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome.
| Type of Mismatch Corrected by MMR | Description |
|---|---|
| Base-Base Mismatches | Incorrect pairing of standard bases (e.g., G paired with T instead of C) |
| Small Insertion/Deletion Loops | Extra nucleotides inserted or nucleotides missing, often from slippage during replication |
For more in-depth information, you can explore resources on DNA mismatch repair mechanisms.
