Link Between DNA Repair and DNA Remodeling Proteins

Michael J. Smerdon, Ph.D.
School of Molecular Biosciences, Washington State University
R37ES002614 and R01ES004106

Two proteins involved in chromatin remodeling interact with nucleotide excision repair damage-recognition proteins to play a key role in enabling cells to repair DNA damage according to a new study by NIEHS-grantee Michael Smerdon and colleagues at Washington State University. Their paper, published is Nature Structural and Molecular Biology was name ”Article of the Month.”

The researchers exposed yeast cells to UV radiation to cause DNA damage, and then studied the actions of several DNA-associated proteins including eleven proteins in a complex called SWI/SNF. SWI/SNF changes the shape and arrangement of DNA with its associated structural proteins. They found that in yeast cells undergoing high rates of DNA repair, SWI/SNF is physically attached to two key proteins involved in recognizing DNA damage-Rad4 and Rad23. In yeast cells with the SWI/SNF complex knocked out, the cells lost the ability to remodel DNA and to repair DNA damage.

Each cell in the human body sustains thousands of DNA lesions each day as a result of normal metabolic activity regardless of lifestyle choices such as smoking, UV exposure, diet, etc. Smerdon and his group are continuing their work in human cells, which contain a SWI/SNF complex that appears to function similarly to the yeast complex. Smerdon is a Method to Extend Research In Time (MERIT) grant recipient from NIEHS; a prestigious grant award given to very few NIEHS grantees.

Implications: Gong F, Fahy D, Smerdon MJ. Rad4-Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with nucleotide excision repair. Nat Struct Mol Biol. 2006 Oct;13(10):902-7.