DNA repair protein XRCC4

Interaction of XRCC4 in NHEJ

File:Mechanism of non-homologous end joining for double-stranded DNA breaks MF.png

Mechanism of non-homologous end joining for double-stranded DNA breaks MF

DNA repair protein XRCC4 is a crucial protein involved in the DNA repair process, specifically in the non-homologous end joining (NHEJ) pathway. This pathway is essential for the repair of double-strand breaks (DSBs) in DNA, which can be caused by factors such as ionizing radiation, oxidative stress, and certain chemotherapeutic agents.

Structure and Function

XRCC4 is a protein encoded by the XRCC4 gene in humans. It forms a complex with DNA ligase IV, a critical enzyme in the NHEJ pathway. This complex is responsible for the final ligation step of the DNA repair process, where the broken DNA ends are joined together. XRCC4 also interacts with other proteins involved in the NHEJ pathway, such as Ku70, Ku80, and Artemis.

The XRCC4 protein has a coiled-coil domain that facilitates its interaction with DNA ligase IV and other NHEJ proteins. This interaction is vital for the stability and function of the DNA repair complex. Mutations or deficiencies in XRCC4 can lead to severe consequences, including genomic instability, increased sensitivity to DNA-damaging agents, and a higher risk of developing cancer.

Role in Disease

Defects in XRCC4 are associated with several human diseases. For instance, mutations in the XRCC4 gene can lead to microcephaly, a condition characterized by a significantly smaller head size and brain development issues. Additionally, XRCC4 deficiencies are linked to immunodeficiency disorders, as the NHEJ pathway is also crucial for the development of the immune system, particularly in the process of V(D)J recombination.

Research and Clinical Implications

Understanding the function and mechanisms of XRCC4 is essential for developing targeted therapies for diseases associated with DNA repair deficiencies. Researchers are exploring potential treatments that can enhance the NHEJ pathway or compensate for the loss of XRCC4 function. These treatments could be particularly beneficial for patients with cancer, as enhancing DNA repair mechanisms can improve the efficacy of certain chemotherapeutic agents.

Related Pages

• DNA repair
• Non-homologous end joining
• Double-strand break
• DNA ligase IV
• Ku70
• Ku80
• Artemis
• Genomic instability
• Cancer
• Microcephaly
• Immunodeficiency
• V(D)J recombination

Y-STR Name

Haplotype