Research Spotlight: NEIL1 and DNA Repair

By Matt Wargo • March 3rd, 2010

Odell ID, Newick K, Heintz NH, Wallace SS, Pederson DS. 2010. Non-specific DNA binding interferes with the efficient excision of oxidative lesions from chromatin by the human DNA glycosylase, NEIL1. DNA Repair (Amst) 9(2):134-43.

Authors’ Association with MMG:
Ian D. Odell – 5th year MD-PhD student in MMG
Kheng Newick – 2nd year PhD student in CMB
Nicholas H. Heintz – adjunct professor in MMG
Susan S. Wallace – department chair of MMG
David S. Pederson – professor in MMG

Humans, as well as all other eukaryotic organisms, compact their DNA ~10,000-fold by folding and wrapping their DNA around core proteins. The basic unit is called a nucleosome, 147 base pairs of DNA wrapped around histone proteins. How DNA-binding proteins, such as transcription factors, are able to find their targets in the context of nucleosomes is a major question in molecular biology. Our lab previously showed that a protein capable of identifying damaged DNA was able to find its target because the nucleosomal DNA unwraps and rewraps for short periods of time, thereby making its target transiently accessible. In this paper, our goal was to find out if the ability to function on nucleosomes was particularly special about this protein. To answer this question, we compared the activity on nucleosomes of two proteins that recognize the same DNA damage. We found out that both proteins are very similar in abundance and activity, but surprisingly, one binds undamaged DNA with significantly higher affinity than the other. Because the cell nucleus contains a vast sea of undamaged DNA, the high affinity likely inhibits its activity on nucleosomes in vivo.

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