Matrix Attachment Regions (MAR/SAR) as Hotspots of Chromosomal Breakage: Mechanistic Insights with Focus on the AF9 Gene

Abstract

Objective: To review current evidence on the structural and functional properties of MAR/SAR sequences and their association with chromosomal breakage, with a specific focus on the AF9 gene and its relevance to translocation events.

Method: A narrative synthesis of published studies examining MAR/SAR characteristics, chromatin architecture, apoptotic nuclease activity, and breakpoint mapping in MLL, AF9, ABL, and other translocationprone genes.

Results: MAR/SAR elements act as preferential cleavage sites during oxidative stress and apoptosis, where nucleases such as CAD target DNA at chromatin loop bases. In the AF9 gene, two MAR/SAR regions (SAR1 and SAR2) flank breakpoint cluster regions implicated in MLL-AF9 fusion formation. Oxidative stress enhances SAR?specific cleavage in nasopharyngeal epithelial cells, while non-SAR breakage is associated with repetitive elements rather than MAR/SAR architecture.

Conclusion: MAR/SAR sequences are essential for chromatin organization but also represent intrinsic fragile sites. Their structural properties help explain susceptibility to chromosomal breakage and the formation of cancer related translocations.