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Cryo-EM structure of the FACT-histone complex


EMSL Project ID
51326

Abstract

The FACT complex, composed of hSpt16 and SSRP1 in human, was initially discovered as a factor that is essential for transcription elongation. It functions as an ATP-independent histone chaperone to facilitate the disassembly and reassembly of nucleosomes in the wake of RNA polymerase II mediated transcription. The FACT complex also has additional roles in DNA replication, DNA repair and mitosis. Consistent with these pleiotropic roles of the FACT complex, its overexpression profoundly impacts chromatin homeostasis mechanisms resulting in diseases such as breast and ovarian cancer. Notably, high levels of FACT expression correlate with the aggressiveness of breast cancer and accelerate tumor proliferation. These observations support the idea that the FACT complex is an oncogenic histone chaperone. Our goal in this project is to identify the orientation and specificity of interactions between the FACT complex and histone subunits by solving a near-atomic resolution cryo-EM structure.

Project Details

Start Date
2020-05-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Uhn-soo Cho
Institution
University of Michigan

Team Members

Byung Chul Kim
Institution
University of Michigan

Nancy Meyer
Institution
Oregon Health & Science University