Nikola P. Pavletich
Memorial Sloan Kettering Cancer Center
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Primary Section: 21, Biochemistry Membership Type:
Member
(elected 2012)
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Research Interests
Nikola Pavletich uses X-ray crystallography in combination with biochemistry and cell biology to address questions in cancer biology. His laboratory's first research focus was the crystal structure of the p53 tumor suppressor, a transcription factor that controls a DNA-damage checkpoint of the cell cycle. His interests then evolved in the general areas of growth-regulatory pathways and genomic integrity. In the cell cycle area, crystal structures determined by his laboratory helped establish the general principles governing the on/off switching of cyclin-dependent kinases, the control of the cell-cycle transcription program by the retinoblastoma protein, and the mechanisms through which ubiquitin ligases catalyze ubiquitination. In genomic integrity, his laboratory found that the BRCA2 tumor suppressor is a single-stranded DNA binding protein that catalyzes the assembly of the RAD51 recombinase on DNA, a rate-limiting step in the repair of DNA breaks by homologous-recombination. This led to their structural work with RecA, the bacterial RAD51 homolog, addressing the mechanism of homologous recombination. More recently, his laboratory has determined structures investigating the recognition of lesions by the Xeroderma Pigmentosum nucleotide-excision repair proteins, and the function of Fanconi Anemia proteins in inter-strand crosslink repair.
