Our lab studies mechanisms of double-strand break (DSB) formation, a cause of genome instability, by combining our innovative experimental method [REF 1] with computational modeling approaches [REF 2].
Despite many studies on the mechanisms of DNA double-strand breaks (DSB) formation, our knowledge of them is very incomplete. To date, DSB formation has been extensively studied only at specific loci but remains largely unexplored at the genome-wide level. This is owing to the lack of systematic, genome-wide studies to objectively test and compare the proposed mechanisms of DSB formation, as well as the lack of high- resolution genome-wide maps of DSBs obtained by direct DSB labeling to validate them. Working with collaborators, we have recently developed a method to label DSBs in situ followed by deep sequencing (BLESS), and used it to map DSBs in human cells with a resolution 2-3 orders of magnitude better than previously achieved. Our results show that hypothesis-driven analysis of high-resolution genomic regions identified by BLESS can help explore the basis of genomic instability genome-wide. Such analysis should eventually allow use of DSB localization signatures for diagnostic and prognostic purposes.
MOST RELEVANT PUBLICATIONS
1. “Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing”, Crosetto, Nicola; Mitra, Abhishek; Silva, Maria Joao; et al., NATURE METHODS 10 (4) (2013), www.breakome.eu
2. “High-resolution timing of cell cycle-regulated gene expression”, Rowicka, Maga; Kudlicki, Andrzej; Tu, Benjamin P.; et al., PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 104 (43), 16892-16897, (2007).