In order to address how DNA lesions within compact states of chromatin are identified, exposed, and ultimately repaired, we constructed a designer chromatin having a unique, multi-functional DNA sequence. This designer chromatin platform enables site-specific incorporation of any DNA lesion, FRET-compatible dyes, RNA binding sequence, or specific binding sequence of transcription factors/chromatin remodelers. Using this system, we are initially focused on Base Excision Repair (BER) because our designer chromatin is an excellent <i>in vitro </i>platform to address the effect of chromatin topology on the repair process. Although BER is a well-defined pathway, details regarding BER within the restrictive environment of chromatin are poorly understood. In order to address this issue, we have studied (for the first time) the BER process and its reactive DNA intermediates within defined chromatin architectures. We show that various ‘extended’ and ‘compact’ states of chromatin significantly influence BER, which is also impacted by the position of the DNA lesion. Our data also show that histone modifications play a role in BER by modulating chromatin structure. These results, as well as the general utility of our model chromatin system, will be presented.

Construction of designer chromatin with unique multi-functional DNA sequence: Effect of chromatin topology in base excision repair

255th National Meeting (2018)

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