Question

Fidelity of Replication of DNA What factors promote the fidelity of replication during synthesis of the leading strand of DNA? Would you expect the lagging strand to be made with the same fidelity? Give reasons for your answers.

Short answer

Both strands have similar fidelity due to proofreading by DNA polymerase, though the lagging strand may have slightly more errors.

Step-by-step solution

Understanding DNA Replication

DNA replication is the process by which a DNA molecule is copied. The leading strand is synthesized continuously, while the lagging strand is synthesized in fragments called Okazaki fragments.

Factors Promoting Fidelity

Fidelity in DNA replication refers to how accurately the new DNA strand is synthesized. Enzymes like DNA polymerase have proofreading abilities, which allow them to remove incorrectly paired nucleotides. The inherent structural properties of DNA also promote correct base pairing.

Proofreading by DNA Polymerase

DNA polymerase is the enzyme responsible for adding nucleotides to the growing DNA strand. It has a proofreading function that corrects errors by removing mismatched nucleotides, enhancing the overall fidelity of DNA synthesis.

Similar Fidelity in Leading and Lagging Strands

Both the leading and lagging strands use the same DNA polymerase with proofreading abilities, ensuring similar fidelity. However, the lagging strand might have a slightly higher error rate due to the additional steps and fragment joining.

Conclusion

The DNA replication machinery ensures high fidelity in both leading and lagging strands, although the complex synthesis of the lagging strand might introduce more errors. Overall, the replication process is very accurate.

Key concepts

DNA Polymerase

DNA Polymerase is an essential enzyme in the process of DNA replication. These enzymes are responsible for adding nucleotides, the building blocks of DNA, to the new DNA strand being synthesized. But DNA polymerase does more than just "add beads to a string." It ensures the right beads (nucleotides) fit together.

One of the remarkable features of DNA polymerase is its precision. It matches each incoming nucleotide with the complementary base on the template strand, thanks to the specific pairing rules (A with T and G with C) in DNA. Furthermore, DNA polymerase is not just a one-type enzyme. There are several different kinds, with each having specific roles in the cell. For example, DNA polymerase III is the main enzyme involved in the DNA replication process in prokaryotes.

Despite the complexity and high speed of replication, DNA polymerase keeps errors to a minimum, which is crucial because errors can lead to mutations and diseases. The enzyme also has a built-in proofreading capability, which acts like a spell-check to ensure the newly synthesized DNA is as accurate as possible.

Proofreading Mechanism

The proofreading mechanism refers to the ability of DNA polymerase to correct its mistakes during DNA replication. You might wonder how the enzyme knows if it added the wrong nucleotide. This mechanism involves the enzyme's ability to sense a mispairing due to a structural kink in the DNA.

When DNA polymerase detects an incorrect nucleotide, it doesn't just move on. Instead, the enzyme uses its exonuclease activity to remove the mismatched base. This is akin to hitting the "backspace" key. Then, the polymerase repositions itself and inserts the correct nucleotide.

Proofreading happens right away, immediately after the incorrect base is added. This swift action is crucial in minimizing errors. Imagine if your autocorrect waited hours before fixing a typo! This effective proofreading ensures that the error rate during replication remains exceptionally low, at approximately 1 in 1 billion bases.

• Immediate correction of errors
• Involves exonuclease activity
• Essential for maintaining genetic stability

Leading and Lagging Strands

DNA replication involves the synthesis of two strands, known as the leading and lagging strands. These strands have slightly different dynamics owing to the directional nature of DNA polymerase, which can only add nucleotides in a 5' to 3' direction.

The leading strand is synthesized continuously because it runs in the same direction as the replication fork's movement. It's like building a straight road without any stops. DNA polymerase can smoothly add nucleotides one after another.

Conversely, the lagging strand is more like a zigzag road, requiring the synthesis of short stretches called Okazaki fragments. Since this strand runs opposite to the fork's progression, DNA polymerase has to wait and work in segments. Each fragment begins with a short RNA primer, which DNA polymerase later extends, then enzymes remove the RNA, and finally, all fragments are joined together by DNA ligase.

• Leading strand: continuous synthesis
• Lagging strand: disjointed synthesis using Okazaki fragments
• Both use the same DNA polymerase, ensuring overall high fidelity