GENOME-WIDE IDENTIFICATION OF DNA REPAIR FACTORS INVOLVED IN CHROMOSOME FRAGILITY DISORDERS

Abstract

Background: Inherited diseases characterized by genomic instability, defective DNA repair pathways and predisposition to cancer and developmental anomalies are called chromosome fragility disorders. Defects in DNA repair pathways, such as homologous recombination, nucleotide excision repair, and double-strand break repair, are major causes of chromosome breakage and cellular dysfunction.

Objective: It sought to identify and characterize genome-wide DNA repair factors associated with chromosome fragility disorders through integrative bioinformatics and genomic analysis approaches.

Methods: Comparative genomics, protein interaction networks and pathway enrichment analyses were performed on genome-wide datasets of DNA repair genes, transcriptomic profiles and mutation databases. Candidate repair factors associated with chromosomal instability were identified by differential expression analysis and functional annotation.

Findings: A total of 214 DNA repair-associated genes were identified and 37 genes were found to be significantly differentially expressed under chromosome stress conditions . Key repair factors including BRCA1, RAD51, ATM and FANCD2 displayed increased mutation frequencies and strong pathway interactions. Functional enrichment analysis revealed that homologous recombination pathways accounted for ~42% of the genomic instability responses identified.

Conclusion: Genome-wide identification of DNA repair factors provides important insights into the molecular mechanisms underlying chromosome fragility disorders and may help future therapeutic strategies for diseases related to genomic instability.