The goal of this research is to understand the relationship between chromatin assembly, chromatin structure and nuclear function. It is clear that chromatin assembly is a fundamental process that is essential for the replication and maintenance of the eukaryotic genome. Following DNA synthesis, the genome must be rapidly and accurately assembled into chromatin to re-establish specific chromatin structures onto the daughter DNA strands. Even subtle changes in chromatin structure can lead to gene dysfunction and to disease states, such as cancer. Despite its obvious global importance, the process of chromatin assembly is poorly understood. The research proposed in Specfic Aim 1 will delineate the chromatin assembly mechanism that is mediated by the putative physiologically relevant chromatin assembly factors RCAF (replication-coupling assembly factor) and CAF- 1 (chromatin assembly factor 1). These experiments will utilize a defined recombinant chromatin assembly system that permits us to detect the contribution that RCAF and CAF- 1 make to each step in the process. These biochemical studies of the chromatin assembly mechanism will be complemented by molecular, cellular, and genetic studies to test the hypothesis that RCAF and CAF- 1 are directly involved in the assembly of chromatin in budding yeast (Specific Aim 2). The unique nature of the biochemical system, coupled with the genetic analyses, will provide a coherent and effective approach in this emerging and exciting new area of chromatin assembly, structure and function. In addition, this work will impact the fields of gene expression, DNA repair, replication and recombination and may provide valuable insight into human disease states, including cancer that involve defects in these important chromatin-utilizing processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064475-02
Application #
6620454
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Carter, Anthony D
Project Start
2002-03-01
Project End
2007-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
2
Fiscal Year
2003
Total Cost
$258,966
Indirect Cost
Name
University of Colorado Denver
Department
Biochemistry
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Pal, Sangita; Postnikoff, Spike D; Chavez, Myrriah et al. (2018) Impaired cohesion and homologous recombination during replicative aging in budding yeast. Sci Adv 4:eaaq0236
Tyler, Jessica K; Johnson, Jay E (2018) The role of autophagy in the regulation of yeast life span. Ann N Y Acad Sci 1418:31-43
Hung, Putzer J; Chen, Bo-Ruei; George, Rosmy et al. (2017) Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-homologous end joining in lymphocytes. Cell Cycle 16:286-295
Postnikoff, Spike D L; Johnson, Jay E; Tyler, Jessica K (2017) The integrated stress response in budding yeast lifespan extension. Microb Cell 4:368-375
Fowler, Faith; Tyler, Jessica K (2017) Anchoring Chromatin Loops to Cancer. Dev Cell 42:209-211
Aguilar, Rhiannon R; Tyler, Jessica K (2017) Thinking Outside the Cell: Replicating Replication In Vitro. Mol Cell 65:5-7
Wang, Pingping; Byrum, Stephanie; Fowler, Faith C et al. (2017) Proteomic identification of histone post-translational modifications and proteins enriched at a DNA double-strand break. Nucleic Acids Res 45:10923-10940
Chen, Kaifu; Hu, Zheng; Xia, Zheng et al. (2016) The Overlooked Fact: Fundamental Need for Spike-In Control for Virtually All Genome-Wide Analyses. Mol Cell Biol 36:662-7
Pal, Sangita; Graves, Hillary; Ohsawa, Ryosuke et al. (2016) The Commercial Antibodies Widely Used to Measure H3 K56 Acetylation Are Non-Specific in Human and Drosophila Cells. PLoS One 11:e0155409
Li, Xuan; Tyler, Jessica K (2016) Nucleosome disassembly during human non-homologous end joining followed by concerted HIRA- and CAF-1-dependent reassembly. Elife 5:

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