Project 1 investigates a novel kind of genetic information that is encoded directly in the genomic DNA sequence, through the sequence-dependent mechanical properties of DNA itself. This information is superimposed directly on top of protein coding and regulatory signals that were previously recognized, and is based on the sequence-dependent mechanical properties of the DNA itself. Genomes can use this information to tune the stability of protein-DNA complexes containing such sharply distorted DNA through constraints on the detailed DNA sequence, even when these DNA sequences are not contacted directly by any proteins. The degeneracy of the genetic code, and of many DNA binding regulatory proteins'target sites, allow this novel sequence-dependent mechanical information to be superimposed, or multiplexed on top of other kinds of genetic information without distortion or cross-interference. Examples of essential biological structures in which DNA is sharply distorted in this way include eukaryotic nucleosomes (in which 75-90% of all eukaryotic DNA is organized), and also many double-strand DNA- (dsDNA-) containing viruses, and many bacterial and eukaryotic protein-DNA gene regulatory complexes. Project 1 combines theoretical and experimental approaches to develop a predictive mechanistic understanding of these fundamentally important sequence-dependent mechanics of DNA.
| Serebryannyy, Leonid A; Yemelyanov, Alex; Gottardi, Cara J et al. (2017) Nuclear ?-catenin mediates the DNA damage response via ?-catenin and nuclear actin. J Cell Sci 130:1717-1729 |
| Shah, M Y; Martinez-Garcia, E; Phillip, J M et al. (2016) MMSET/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents. Oncogene 35:5905-5915 |
| Voong, Lilien N; Xi, Liqun; Sebeson, Amy C et al. (2016) Insights into Nucleosome Organization in Mouse Embryonic Stem Cells through Chemical Mapping. Cell 167:1555-1570.e15 |
| Serebryannyy, Leonid A; Cruz, Christina M; de Lanerolle, Primal (2016) A Role for Nuclear Actin in HDAC 1 and 2 Regulation. Sci Rep 6:28460 |
| Hill, Steven M; Heiser, Laura M; Cokelaer, Thomas et al. (2016) Inferring causal molecular networks: empirical assessment through a community-based effort. Nat Methods 13:310-8 |
| Zhao, Baobing; Mei, Yang; Schipma, Matthew J et al. (2016) Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening. Dev Cell 36:498-510 |
| Serebryannyy, Leonid A; Parilla, Megan; Annibale, Paolo et al. (2016) Persistent nuclear actin filaments inhibit transcription by RNA polymerase II. J Cell Sci 129:3412-25 |
| Chuang, Yishan; Hung, Michelle E; Cangelose, Brianne K et al. (2016) Regulation of the IL-10-driven macrophage phenotype under incoherent stimuli. Innate Immun 22:647-657 |
| Kreamer, Naomi N; Phillips, Rob; Newman, Dianne K et al. (2015) Predicting the impact of promoter variability on regulatory outputs. Sci Rep 5:18238 |
| Mulligan, Peter J; Chen, Yi-Ju; Phillips, Rob et al. (2015) Interplay of Protein Binding Interactions, DNA Mechanics, and Entropy in DNA Looping Kinetics. Biophys J 109:618-29 |
Showing the most recent 10 out of 161 publications
