ESHRE

Overview

ERCC8 (Excision Repair Cross-Complementation Group 8) is a gene that encodes a protein involved in the nucleotide excision repair (NER) pathway, which is crucial for repairing DNA damage caused by ultraviolet (UV) light and other mutagens. The ERCC8 protein is also known as Cockayne syndrome group A protein (CSA), and mutations in this gene are associated with Cockayne syndrome, a rare autosomal recessive disorder characterized by growth failure, neurological degeneration, and photosensitivity.

Function

The ERCC8 gene is located on chromosome 5q12.1 and encodes a protein that plays a critical role in the transcription-coupled repair (TCR) sub-pathway of NER. The CSA protein is part of a complex that recognizes and repairs transcription-blocking lesions in DNA. It interacts with other proteins, such as ERCC6 (also known as Cockayne syndrome group B protein or CSB), to facilitate the removal of damaged DNA and the resumption of transcription.

Clinical Significance

Mutations in the ERCC8 gene can lead to Cockayne syndrome type A (CSA), which is characterized by:

• Growth retardation
• Neurological impairment
• Photosensitivity
• Premature aging

Patients with Cockayne syndrome often exhibit developmental delays, microcephaly, and progressive neurological decline. The severity of symptoms can vary, and the condition is typically diagnosed in early childhood.

Molecular Pathology

ERCC8 mutations result in a defective CSA protein, which impairs the TCR process. This leads to the accumulation of DNA damage, particularly in actively transcribed genes, contributing to the clinical manifestations of Cockayne syndrome. The inability to effectively repair DNA damage results in increased cellular apoptosis and tissue degeneration.

Research and Therapeutic Approaches

Research into ERCC8 and its role in DNA repair continues to be an active area of study. Understanding the molecular mechanisms of ERCC8 function and its interactions with other repair proteins may provide insights into potential therapeutic strategies for Cockayne syndrome and related disorders. Gene therapy and small molecule drugs that enhance DNA repair pathways are potential areas of therapeutic development.

Also see

• Cockayne syndrome
• Nucleotide excision repair
• DNA repair
• ERCC6
• Photosensitivity disorders