ERCC5

ERCC5 (Excision Repair Cross-Complementation Group 5) is a protein that in humans is encoded by the ERCC5 gene. This protein is essential for the repair of DNA damage, specifically in the process of nucleotide excision repair (NER). NER is a critical mechanism by which cells fix mutations caused by ultraviolet (UV) light or chemical mutagens, thereby preventing skin cancer, aging, and other DNA damage-related conditions.

Function

The ERCC5 protein, also known as XPG, plays a dual role in the NER pathway. It acts as a structure-specific endonuclease that makes the 3' incision during the excision of the DNA lesion. Additionally, ERCC5 is involved in the repair synthesis step of NER, where it interacts with other NER proteins to ensure accurate repair of the DNA. This protein is also implicated in the repair of DNA double-strand breaks and in the process of homologous recombination, highlighting its importance in maintaining genomic stability.

Clinical Significance

Mutations in the ERCC5 gene are associated with a range of disorders related to defective DNA repair mechanisms. These include Xeroderma Pigmentosum, which is characterized by an extreme sensitivity to sunlight leading to skin cancer, and Cockayne Syndrome, a disorder causing growth failure, premature aging, and neurological abnormalities. Understanding the function and pathology related to ERCC5 is crucial for the development of therapeutic strategies for these conditions.

Genetic Structure

The ERCC5 gene is located on the long (q) arm of chromosome 13 at position 33, specifically 13q33.1. The gene spans over 19 kilobases and consists of several exons that encode the ERCC5 protein. The genetic structure of ERCC5 has been extensively studied to understand its role in DNA repair and its implications in genetic disorders.

Research and Therapeutic Approaches

Research on ERCC5 has led to significant advancements in understanding DNA repair mechanisms. Therapeutic approaches targeting the NER pathway, and specifically the function of ERCC5, are being explored for the treatment of cancer and other diseases resulting from DNA repair defects. Small molecule inhibitors and gene therapy are among the strategies being investigated to enhance or correct ERCC5 function in disease contexts.

See Also

• Nucleotide excision repair
• DNA repair
• Xeroderma Pigmentosum
• Cockayne Syndrome