Question

What is the difference between nonhomologous end-joining (NHEJ) and homology- directed repair (HDR) in the context of genome editing?

Short answer

Explain the difference between nonhomologous end-joining (NHEJ) and homology-directed repair (HDR) in the context of genome editing. Nonhomologous end-joining (NHEJ) is an error-prone DNA repair mechanism that fixes double-strand breaks (DSBs) by directly ligating the broken ends without a homologous template. This process can cause gene disruptions or mutations due to the insertion or deletion of nucleotides. In contrast, homology-directed repair (HDR) is a more accurate DNA repair mechanism that utilizes a homologous template, such as a sister chromatid, to repair DSBs precisely by copying the original sequence. In genome editing, NHEJ is more common and efficient but may introduce unwanted mutations, while HDR is less efficient but ensures precise gene editing using a provided homologous template.

Step-by-step solution

Briefly describe nonhomologous end-joining (NHEJ)

Nonhomologous end-joining (NHEJ) is one of the major DNA repair pathways. It is an error-prone process that repairs double-strand breaks (DSBs) in DNA by directly ligating the broken ends together, without any homologous template. The process may cause insertion or deletion of nucleotides, which may lead to gene disruptions or mutations.

Briefly describe homology-directed repair (HDR)

Homology-directed repair (HDR) is an alternate DNA repair mechanism that relies on a homologous DNA template, usually a sister chromatid, to precisely repair double-strand breaks (DSBs). The process is more accurate compared to NHEJ, as it restores the original DNA sequence by copying the information from the homologous template.

Compare NHEJ and HDR in the context of genome editing

In the context of genome editing, both NHEJ and HDR pathways can be used to achieve specific gene modifications. However, the choice between these repair mechanisms is based on their efficiency, the desired outcome, and the availability of a homologous template. NHEJ is more commonly used in genome editing because it is faster and more efficient in repairing DSBs. However, it is error-prone and may introduce unwanted mutations. HDR, on the other hand, is preferred when precise gene editing is needed, as it ensures that the desired modification is introduced accurately using a provided homologous template. But HDR is less efficient compared to NHEJ, and its efficiency can be cell-type and cell-cycle dependent. So, the main differences between NHEJ and HDR in the context of genome editing are: 1. NHEJ is an error-prone repair mechanism that doesn't require a homologous template, while HDR is a more accurate repair mechanism that uses a homologous template. 2. NHEJ is faster and more efficient in repairing DSBs but may result in unwanted mutations; on the other hand, HDR is less efficient but useful for precise gene editing.