Areas of Specialty

Research in the Osley laboratory is focused on the role of chromatin in gene expression, DNA replication, and DNA double-strand break repair. We use the model organism, Saccharomyces cerevisiae, to investigate these cellular processes in quiescent cells, which represent nongrowing but viable cells that are in the G0 phase of the cell cycle.osley-1.jpeg

The epigenome of quiescent cells: Using genomic approaches, our recent studies focused on the role of chromatin in the development of quiescent cells that are formed in stationary phase following the depletion of glucose. These studies showed the retention of several histone methylation marks and RNA polymerase II on inactive genes in quiescent cells, suggesting that the epigenome of quiescent cells poises these cells to resume growth when nutrients are restored.

Quiescent yeast cells are also an excellent model for the study of chronological lifespan. We are performing a genetic screen for histone modification mutants to identify histone post-translational modifications that are required for the development of quiescent cells and their long-term survival.

DNA replication program of quiescent cells: Quiescent cells re-enter the cell cycle and resume division when glucose is restored. Using molecular, genetic and genomic approaches, we are defining the program that initiates DNA replication in quiescent G0 cells under these conditions and comparing it to the program that occurs when G1 cells enter S phase. Our data have found significant differences in the DNA initiation programs between G1 and G0 cells.

DNA repair in quiescent cells: Quiescent cells are resistant to many DNA damaging agents but are more sensitive to UV irradiation than growing cells and accumulate more mutations in their genome. We are performing molecular, genetic and genomic analyses to define the pathways and mechanisms that contribute to increased UV-induced mutagenesis in these cells.

Key Publications

Young, CP, Hillyer, C, Hokamp, K, Fitzpatrick, DJ, Konstantinov, NK, Welty, JS, Ness, SA, Werner-Washburne, M, Fleming, AP, and Osley, MA: Distinct histone methylation and transcription profiles are established during the development of cellular quiescence in yeast.  BMC Genomics. Jan 26;18(1), 2017.

Wiest, NE, Houghtaling, S, Sanchez, JC, Tomkinson, AE, and Osley, MA. The SWI/SNF ATP-dependent nucleosome remodeler promotes resection initiation at a DNA double-strand break in yeast. Nucleic Acids Research 45: 5887-5900, 2017.

Trujillo, KT and Osley, MA: A role for H2B ubiquitylation in DNA replication, Mol Cell, 48: 734-746, 2012.

Shieh, GS, Pan, C-H, Wu J-H, Sun, Y-J, Chang, K-W, Tung, L, Chang, T-H, Fleming, A, Hillyer, C, Berger, SL, Osley, MA* and Kao, C-K*: H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast. BMC Genomics. Dec 22;12(1): 627 [epub ahead of print], 2011.

Houghtaling, S, Tsukuda, T, and Osley, MA: Molecular assays to investigate chromatin changes during DNA double-strand break repair in yeast. Methods in Molecular Biology, 745: 79-97, 2011.

Nakanishi, S, Lee, JS, Gardner, JM, Takahashi, Y, Chandrasekharan, Sun, ZW, Osley, MA, Strahl, B, Jasperson, SL, Shilatifard, A: Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1. J Cell Biol, 186: 371-377, 2009.

Tsukuda, T, Lo, Y-C, Krishna, S, Sterk, R, Osley, MA, and Nickoloff, J: INO80-dependent chromatin remodeling regulates early and late stages of mitotic homologous recombination. DNA Repair, 8: 360-360, 2009.

Fleming, AB, Kao, C-F, Hillyer, C, Pikaart, M, and Osley, MA: H2B ubiquitylation plays a role in nucleosome dynamics during transcription elongation. Mol Cell, 31: 57-66, 2008.

Xiao, X, Kao, CK, Krogan, N, Greenblatt, J, Sun, ZW, Osley, MA, and Strahl, B: Rad6-dependent ubiquitylation of H2B is associated with elongating RNA polymerase II.  Mol. Cell. Biol. 25: 637-651, 2005.

Tsukuda, T, Fleming, A, Nickoloff, J.A, and Osley, MA: Chromatin remodeling at a DNA double-strand break site in Saccharomyces cerevisiae. Nature 438: 379-383, 2005.