Research Interests

The genomic DNA of eukaryotes is packaged into chromatin through a fundamental repeating unit known as the nucleosome. In this chromatin environment, our genomic DNA is constantly exposed to a variety of endogenous and exogenous sources of DNA damage. This DNA damage must be effectively repaired to prevent mutagenesis, genomic instability, and human disease (e.g. cancer). Importantly, the nucleosome and higher-order chromatin structure are key regulatory barriers that must be overcome to successfully repair DNA damage and maintain genome stability. How DNA repair proteins overcome this barrier to repair and the role of chromatin-modifying enzymes in facilitating DNA repair pathways remains poorly understood. 

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The overarching goal of the Weaver Lab is to determine mechanisms of DNA repair in the context of chromatin, and harness these mechanistic insights to improve human health. Current research projects in the lab aim to address several fundamental questions at the interface of the DNA repair and chromatin biology fields: ​

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1. How does DNA damage impact chromatin structure, stability, and dynamics?

2. How do DNA repair enzymes identify and process DNA damage in chromatin? 

3. How do chromatin-modifying enzymes regulate chromatin structure to facilitate DNA repair?

4. Can we harness these mechanistic insights to target DNA repair enzymes and/or chromatin-modifying enzymes in human disease?

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The lab addresses these questions using a reductionist approach, where we reconstitute DNA repair in chromatin in vitro using a powerful combination of biochemistry, single-molecule fluorescence microscopy, structural biology, and cell biology techniques.