Question

DNA Repair Mechanisms Vertebrate and plant cells often methylate cytosine in DNA to form 5-methylcytosine (see $\underset{―}{\text{ Fig. }}$ 8-5a). In these same cells, a specialized repair system recognizes $\mathrm{G}-\mathrm{T}$ mismatches and repairs them to $\mathrm{G}\equiv \mathrm{C}$ base pairs. How might this repair system be advantageous to the cell? (Explain in terms of the presence of 5-methylcytosine in the DNA.)

Short answer

The repair system corrects G-T mismatches from methylation, preventing mutations and maintaining genomic integrity.

Step-by-step solution

Understand Methylation

Cells often methylate cytosine to form 5-methylcytosine. This modification can affect gene expression and maintain genome stability. However, during DNA replication or exposure to mutagens, methylated cytosines can spontaneously deaminate, converting into thymine, creating a G-T mismatch.

Recognize the Mismatch Problem

When deamination of 5-methylcytosine occurs, it leads to a G-T mismatch. If not corrected, this mismatch can result in a permanent mutation after DNA replication, as the incorrect base pair may be propagated.

Role of Specialized Repair System

The specialized repair system in question recognizes G-T mismatches and converts them back to G-C base pairs. This system preferentially replaces the thymine with a cytosine, effectively reversing the erroneous mutation caused by deamination.

Consider the Advantage

This repair mechanism is advantageous because it enhances genomic integrity by correcting potentially mutagenic changes. It prevents the propagation of mutations that could arise from natural or chemically induced deamination of 5-methylcytosine.

Key concepts

5-methylcytosine

In vertebrate and plant cells, 5-methylcytosine is formed when cytosine is methylated. This methylation is a key epigenetic modification that can influence gene expression.
It plays a crucial role in regulating genes without altering the DNA sequence itself.
Methylation typically occurs in the context of CpG dinucleotides and is essential for:

• Maintaining cellular identity by silencing genes that are not needed in a particular cell type.
• Mediating developmental processes by signaling which genes should be expressed at different stages.
• Protecting the genome from instability by contributing to the repair and structural integrity of the DNA.

Despite its importance, when 5-methylcytosine is deaminated, it can turn into thymine. This change could lead to incorrect base pairing if not repaired promptly, emphasizing the need for effective repair mechanisms.

G-T mismatch repair

A G-T mismatch arises when a guanine in DNA erroneously pairs with a thymine instead of a cytosine. This can occur due to the deamination of 5-methylcytosine, leading to potential mutations.
This mismatch requires immediate correction to avoid propagation. The specialized repair system recognizes the mispairing and corrects it by replacing the thymine with the correct cytosine. Here’s how it works:

• First, the repair proteins detect the G-T mismatch as an error that needs correction.
• These proteins initiate a repair process, recruiting a specific enzyme that excises the incorrect thymine base.
• Finally, the enzyme replaces the thymine with a cytosine, restoring the correct G-C base pair.

By correcting G-T mismatches, this repair system prevents mutations that could lead to genetic disorders or diseases like cancer. It is an essential mechanism for maintaining genetic fidelity during cell division and DNA replication.

genome stability

Genome stability refers to the ability of a cell's genome to maintain its structure and function over time, which is crucial for the accurate transmission of genetic information.
Several factors contribute to achieving and maintaining genome stability:

• Correct DNA methylation patterns, such as the formation of 5-methylcytosine, help regulate gene expression and maintain genome integrity.
• Efficient repair mechanisms, like the G-T mismatch repair, help correct errors that arise from DNA damage or replication mistakes.
• The stability of the genome is also supported by chromatin organization, which provides structural support and regulates access to the DNA.

Without these elements, cells would accumulate mutations that could compromise their function and viability. Thus, maintaining genome stability is essential for preventing diseases and ensuring the healthy evolution of organisms.