Paz Luncsford – Vellanki, MD/Ph.D.


Chemistry and Biochemistry 2011

Area of Doctoral Study: Biochemistry
Undergraduate Institute: University of Maryland , Baltimore County

Research Advisor: Eric Toth, Ph.D.

Current Position: Hematology-Oncology Fellow,  Johns Hopkins Hospital

Description of Research

The DNA glycosylase MutY homologue (MYH) removes adenines misincorporated opposite 8-oxoguanine as part of the base excision repair (BER) pathway. Importantly, defects in human MYH (hMYH) activity cause the inherited colorectal cancer syndrome, MYH-associated polyposis (MAP). Some hMYH variants likely promote oncogenesis because of their impaired interactions with cellular proteins such as the Rad9-Rad1-Hus1 heterotrimer (the 9-1-1 complex), which mediates the cell-cycle checkpoint response, and AP Endonuclease 1(APE1), the next enzyme in the BER pathway. By solving the crystal structure of the catalytic domain of hMYH and completing in vitro and in vivo assays on S. pombe fission yeast MYH, we have determined that the MYH/9-1-1 interaction is an important step in DNA repair. New data from NMR titration and ITC experiments are helping us to further understand the biochemical interaction between hMYH and APE1.