Lucy F. Pemberton, PhD
Chromatin assembly and genetic instability
The proper assembly of nucleosomes is critical for maintaining genomic stability in all eukaryotic cells. The Pemberton laboratory uses the yeast Saccharomyces cerevisiae to understand how the nuclear import of histones from the cytoplasm is coordinated with DNA synthesis in the nucleus, and how their assembly together is regulated. The lab uses genetic, biochemical and cell biological techniques to address fundamental questions relating to the mechanisms of nucleocytoplasmic transport and chromatin assembly and has made extensive use of the DNA Science core for sequencing. Recent findings from the lab have shown that the evolutionarily conserved chromatin assembly factor, Nap1p helps dedicated nuclear import factors mediate the nuclear import of histones H2A and H2B. Once in the nucleus Nap1p promotes assembly of H2A and H2B into nucleosomes. Nap1p is also a cyclin B-binding protein and plays a role in mitotic progression. How Nap1p regulates these separate functions is not known. The laboratory is currently determining whether the various functions of Nap1p are regulated by phosphorylation, and whether Nap1p plays key roles in modulating transcription elongation. This work is in collaboration with another Cancer Center investigator, Dr. Donald Hunt. In metazoan cells Nap1p appears to be central to the regulation of many essential processes including the maintenance of genomic integrity, cell division, and cellular differentiation. In addition, NAP1 is a member of a large gene superfamily, including SET and TSPY. In humans, mutations and aberrant expression of genes encoded by members of this family correlate with increased occurrence of certain cancers. This suggests that an understanding of the function of Nap1p in a simple model system is relevant to understanding of the development of cancer.