MRE11A: A Potential Drug Target and Biomarker for Double-strand Break Repair

Target Name: MRE11

NCBI ID: G4361

MRE11

MRE11A: A Potential Drug Target and Biomarker for Double-strand Break Repair

Introduction

Double-strand break repair (DSP) is a critical DNA repair process that ensures the stability of genetic material in the cell. When DNA double-strand breaks, the cell needs to repair the broken site through a series of proteins. MRE11A is a double-strand break repair protein that plays an important role in the cellular DNA repair process. Mutations in MRE11A will cause the DNA double strands to fail to be repaired correctly, leading to the occurrence of genetic diseases. Therefore, studying the role of MRE11A in DNA repair and disease is of great significance for the prevention and treatment of genetic diseases. This article will introduce the role, biological function and possibility of MRE11A as a drug target.

The role of MRE11A

MRE11A is an 11kDa protein consisting of two subunits, each consisting of 764 amino acids. The main function of MRE11A is to catalyze the repair process of DNA double strands. In the process of cellular DNA repair, MRE11A mainly participates in two key steps: 1) repairing single-strand damage to DNA double-strands; 2) guiding DNA polymerase III (APIII) to repair along the single strand.

The role of MRE11A in the DNA repair process can be explained by the following aspects:

1. Catalyze the repair of DNA double strands

MRE11A is a DNA repair enzyme that can catalyze the repair process of DNA double strands. After DNA double-strand breaks, MRE11A provides a substrate for DNA polymerase III by binding to single-stranded DNA and guiding it to the repair position of the DNA double-strand. Under the action of DNA polymerase III, MRE11A pairs mismatched bases with complementary bases on single-stranded DNA to form a new DNA strand.

2. Guide DNA polymerase III to repair single-stranded DNA damage

MRE11A can also participate in the DNA repair process by guiding DNA polymerase III to repair single-stranded DNA damage. When DNA double-strand breaks occur, MRE11A can guide single-stranded DNA to the action of DNA polymerase III, thereby repairing single-stranded DNA damage. This type of repair is critical for maintaining genome stability, as many genetic diseases are associated with damage to DNA double strands.

3. Participate in the repair of DNA double strands

MRE11A can also directly participate in the DNA double-strand repair process. During the DNA double-strand repair process, MRE11A can bind to DNA polymerase III, provide a substrate for DNA polymerase III, and participate in the DNA double-strand repair process. The binding of MRE11A enables DNA polymerase III to repair DNA double-stranded damage more effectively, thereby improving the efficiency of DNA double-stranded repair.

Biological functions of MRE11A

MRE11A's role in DNA repair makes it a potential drug target. By inhibiting the activity of MRE11A, the efficiency of DNA repair can be reduced, resulting in double-stranded DNA damage. This damage is an important factor in many genetic diseases, such as cancer, neurodegenerative diseases, immune deficiencies, etc. Therefore, studying the role of MRE11A is of great significance for the development of drugs to treat these diseases.

Potential as a drug target

As an important DNA repair enzyme, MRE11A can be studied as a drug target. Currently, researchers are exploring the possibility of inhibiting MRE11A activity to treat genetic diseases. For example, some research teams are studying the use of drugs to inhibit the activity of MRE11A to treat cancer, especially leukemia. Additionally, some researchers are studying the use of MRE11A as a gene therapy

Protein Name: MRE11 Homolog, Double Strand Break Repair Nuclease

Functions: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11 (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). RAD50 may be required to bind DNA ends and hold them in close proximity (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289, PubMed:30612738). The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888)

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