NIA Interlab: Dissecting novel genoprotective roles of CSB in the epigenome network

National Institute On Aging

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Abstract

CS cells exhibit elevated Poly(ADP)ribose. Thus, one outstanding questions is where in the nucleus does the poly-ADP ribose (PAR) signal originate from. The recently developed ADPr-ChAP mapping of PAR has demonstrated that oxidative damage-induced PAR mostly occurs in heterochromatin regions. Since PAR occurs on heterochromatin, we hypothesize that the heterochromatin structure provides a barrier protecting nuclear DNA from damage. Interestingly, we have found that CS deficient cells have decreased heterochromatin, despite harboring elevated PAR on chromatin, thus potentially rendering their genomes more susceptible to genome instability. By genome-wide deep sequencing of pH2A.X, H3K9me3 and PAR, we expect to identify the genomic hotspot of PAR and analyze the resulting transcriptome alterations in CS.