Question

What are the two main mechanisms by which cells repair doublestrand breaks? Briefly deseribe each one.

Short answer

The two main mechanisms by which cells repair double-strand breaks are Homologous Recombination, which uses the sister chromatid as a repair template and is highly accurate, and Non-Homologous End Joining, which quickly joins the DNA ends but often leads to the loss or addition of a few base pairs.

Step-by-step solution

Identify the Double-Strand Break Repair Mechanisms

The two main mechanisms by which cells repair double-strand breaks are Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ).

Describe Homologous Recombination

Homologous Recombination (HR) is a mechanism for repairing double-strand DNA breaks. This process uses sister chromatid as a repair template. The damaged DNA is cut back with special nucleases, revealing single-stranded DNA. This is then invaded by the undamaged sister chromatid, using its sequence to guide repair, resulting in a perfect repair.

Describe Non-Homologous End Joining

Non-Homologous End Joining (NHEJ) is another mechanism by which cells repair double-strand breaks in DNA. This process brings together the two ends of the DNA fragments without the need for a homologous template, often resulting in the loss or addition of a few base pairs. This is a quicker but less accurate method of repair.

Key concepts

Homologous Recombination

Cells have ingenious systems for fixing DNA breaks, and one of the most precise ways is through Homologous Recombination (HR). Imagine you have a broken zipper, but you have another identical zipper available to guide the repair. HR works similarly. It uses the sister chromatid, an identical copy of the DNA, as a template.

• The damaged DNA strands are trimmed back to reveal single-stranded segments by special proteins called nucleases.
• These segments "invade" the sister chromatid—the intact, identical strand of DNA—and pair with its sequence.
• The missing or damaged sequence is "copied" from the sister chromatid, ensuring the repaired DNA is error-free.

This method is highly accurate because it uses an identical sequence as a guide, resulting in precise repair. However, HR is mainly utilized during the later stages of cell division when an identical sister chromatid is available.

Non-Homologous End Joining

Non-Homologous End Joining (NHEJ) is another way cells fix double-strand breaks, but it’s a bit like a quick fix handyman. Unlike Homologous Recombination, NHEJ doesn't require an identical template. Instead, it swiftly joins the broken ends of DNA. Here’s how it works:

• The break is detected, and the specialized proteins bind to the DNA ends.
• These proteins stimulate a "patchwork" process, bringing the ends together.
• Often, this means adding or losing a few base pairs, leading to a slightly modified DNA sequence.

This method is faster but less precise compared to HR. It is often employed when there is no sister chromatid available, such as in non-dividing cells. Despite its accuracy trade-off, NHEJ is crucial for constant cell survival and maintaining genomic stability.

Double-Strand Break Repair

Double-strand breaks (DSBs) are serious damages to the DNA, akin to a snapped rope. Understanding and fixing these breaks is essential for cellular integrity and preventing mutations.
DSB repair ensures the cell's survival and genomic stability, involving two main pathways: Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ). When a double-strand break occurs, the cell acts swiftly to select the most appropriate repair mechanism based on its current state. This decision is influenced by factors like the cell cycle stage and the availability of sister chromatids.
These repair mechanisms help prevent problems such as cancer or cell death by ensuring that DNA sequences remain as intact and accurate as possible. Understanding DSB repair is crucial for advances in genetic research and therapies aiming to tackle genetic diseases.