Question

Consequence of Nucleotide Substitutions Suppose deoxycytidine (C) in one strand of DNA is mistakenly replaced with deoxythymidine (T) during cell division. What is the consequence for the cell if the deoxynucleotide change is not repaired?

Short answer

Unrepaired deoxycytidine to deoxythymidine substitution can cause a mutation after replication, potentially leading to altered or nonfunctional proteins.

Step-by-step solution

Understand the substitution

In DNA, the base pairs consist of adenine-thymine (A-T) and guanine-cytosine (G-C). A substitution occurs when deoxycytidine (C) in one strand is replaced by deoxythymidine (T). This change results in a mismatched base pair because deoxythymidine typically pairs with adenine.

Recognize the resulting mismatch

Because the original cytosine was replaced by thymine, instead of forming a pair with guanine (C-G), thymine (T) is mismatched with guanine (G). This creates a T-G pairing that is not correct according to the usual base pairing rules.

Predict the replication outcome

If the mismatch is not repaired before the next round of DNA replication, the incorrect base pair can lead to mutations. At the site of T-G mismatch, one strand will lead to a T-A pair while the other will result in a G-C pair post replication, introducing potential mutations in the daughter strands.

Consider the impact on the protein

The mutation can alter the mRNA sequence during transcription if this region encodes a gene, potentially leading to an altered amino acid sequence of the protein. This could affect the protein's function, structural stability, or lead to a nonfunctional protein altogether.

Key concepts

Nucleotide Substitution

Nucleotide substitution is a change that occurs in the DNA sequence where one nucleotide is replaced by another. This specific change can have significant biological consequences.
In the context of DNA, nucleotides are the building blocks that make up the strands of DNA. They contain a sugar, a phosphate group, and a nitrogenous base. The most common bases in DNA include adenine (A), thymine (T), cytosine (C), and guanine (G).
When a nucleotide substitution occurs, such as cytosine (C) being replaced by thymine (T), it can disrupt the normal base pairing rules. Normally, cytosine pairs with guanine (G), but if replaced by thymine, it attempts to pair with adenine (A), or in this mishap, might incorrectly pair with guanine (G). This alteration can lead to mismatches and potentially cause mutations if not corrected.

Base Pair Mismatch

A base pair mismatch occurs when two nucleotides on opposite strands of DNA do not follow the typical pairing rules. In DNA, the established pairings are adenine with thymine (A-T), and cytosine with guanine (C-G).
If a substitution replaces a cytosine with a thymine and pairs it with guanine, a mismatch forms. This results in a T-G mispairing, which the cell recognizes as an error because it disturbs the stability and uniform structure of the DNA helix.
Base pair mismatches can be problematic as they may lead to errors during DNA replication if they go unrepaired. The mechanism that detects and attempts to correct these mismatches is known as the mismatch repair system. This system's failure can allow such errors to persist, eventually resulting in genetic mutations.

Genetic Mutation Consequences

Genetic mutations, like those caused by nucleotide substitutions and base pair mismatches, can have varied consequences for the organism.
A mutation in a non-coding region might go unnoticed, but if it occurs within a gene, it can change the sequence of the encoded protein. This change might alter the protein’s shape and way it functions.

• If the mutation leads to a beneficial trait, it may become prevalent in a population.
• Harmful mutations can result in diseases or malfunctions like cancer.
• Neutral mutations might not impact the organism negatively or positively.

The severity of a mutation's impact depends on its location in the genome and the importance of the affected protein’s role in cellular processes.

Protein Synthesis Impact

Mutations can significantly impact protein synthesis, especially those within coding regions of DNA. During protein synthesis, DNA is transcribed into mRNA, which is then translated into a protein.
If a nucleotide substitution mutation leads to a change in the mRNA sequence, the resulting proteins might have an altered amino acid sequence.

• This can lead to a change in protein function, possibly making it nonfunctional or less effective.
• In some cases, this new amino acid might cause the protein to fold improperly, further affecting its stability and function.
• Sometimes, a single change might be enough to create a stop codon, prematurely ending the protein synthesis. This results in a truncated, usually nonfunctional protein.

Such alterations underscore the critical nature of precise DNA replication and repair mechanisms to ensure proper protein synthesis and function.