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Sang Eun Lee, Ph.D. Repair of double strand breaks in DNA protects organisms by maintaining the integrity of their genomic structures. Double strand breaks occur in chromatin, the tightly wound complex of DNA and associated proteins known as histones that enables DNA to fit into a smaller volume within the cellular nucleus. Previous research has implicated histone modification and chromatin remodeling in the recognition and repair of double strand breaks; however, the nature of the remodeling and how it affects double strand break repair is not fully understood. NIEHS-grantee Sang Eun Lee and colleagues at the University of Texas Health Science Center in San Antonio recently discovered a chromatin alteration caused by a single double strand break generated by an enzyme known as Ho endonuclease. The experiments were carried out using Saccharomyces cerevisiae, a well-known yeast model. The break causes rapid migration of nucleosomes to the damage site which form histone-free DNA 200-300 base pairs in length adjacent to the break. Additional experiments determined that blocking a key chromatin structure remodeling complex (RSC) or deleting RSC2 severely reduced chromatin remodeling. Ionizing radiation and oxidative free radicals, agents humans are exposed to every day, can cause breaks in both strands of DNA. Double strand breaks are the most serious type of DNA damage because neither strand is able to provide physical integrity or information as is the case for single-stranded DNA damage. The investigators conclude that RSC is vital for efficient double strand break repair by mediating chromatin remodeling at the site of the break and allowing the repair machinery access. Citation: Shim EY, Hong SJ, Oum JH, Yanez Y, Zhang Y, Lee SE. RSC mobilizes nucleosomes to improve accessibility of repair machinery to the damaged chromatin. Mol Cell Biol. 2007 Mar;27(5):1602-13. |
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