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Functional networks and cancer roles of the essential histone chaperone FACT (SilentFACT)

  • Sprecher: Professor Dr. Andreas Ladurner
  • Einrichtung: Adolf-Butenandt-Institut
  • Förderung: 2015 bis 2017

We are interested in so-called histone chaperones, which control the assembly and reorganization of eukaryotic chromatin by promoting access to the DNA template, as well as catalysing the deposition or eviction of histones during replication, transcription and DNA repair. They directly bind histone proteins and carry out their genome maintenance function by shielding unfavourable DNA–histone interactions, preventing unspecific aggregation or aiding histone incorporation into nucleosomes.

Mechanistic insight into genome-maintenance catalysed by the histone chaperone FACT

The multisubunit FACT (Facilitates Chromatin Transcription) complex, which is composed of the subunits Spt16 and SSRP1 (encoded by Pob3 and Nhp6 in fungi), is the only essential histone chaperone in S. cerevisiae. It facilitates RNA polymerase II-mediated transcriptional elongation and DNA replication, promotes histone dynamics and is vitally required for the proper assembly of chromatin structure. Over the last few years, we discovered that the Pob3 subunit is required to maintain a fully functional heterochromatin structure at fission yeast centromeres. We identified and characterized a histone H3-H4 binding function residing in the N-terminal aminopeptidase-like fold of the Spt16 subunit and solved its high-resolution crystal structure. We are now comprehensively dissecting the histone chaperoning functions of the FACT complex. In the future, we plan to extend our work to obtain the high-resolution structure of the complex between FACT and histones H2A-H2B.

Quelle: Biomedical Center LMU Physiological Chemistry