WSU Researchers Find Crucial Step In DNA Repair

August 21, 2014

Image Caption: This is Peng Mao in his lab in the WSU School of Molecular Biosciences. Credit: Rebecca E. Phillips

Becky Phillips, Washington State University

Scientists at Washington State University have identified a crucial step in DNA repair that could lead to targeted gene therapy for hereditary diseases such as children of the moon and a common form of colon cancer. Such disorders are caused by faulty DNA repair systems that increase the risk for cancer and other conditions.

The findings are published in this weeks Proceedings of the National Academy of Sciences. The study was funded by the National Institute of Environmental Health Sciences. Regents Professor Michael Smerdon and post-doctoral researcher Peng Mao found that when DNA is damaged, a specific protein must first be unbuckled to allow easy access for the DNA repair crew. Without this unbuckling, entry to the damaged site is hampered by the compact arrangement of genes and protein in chromosomes called chromatin. Smerdon and Maos finding is one of the first to document details of how this repair process takes place in chromatin.

Daily demands for DNA repair

Each human cell sustains a range of assaults that can create up to 100,000 DNA injuries every day, said Smerdon. The cells must repair this damage by continuallyand quicklyproducing replacement DNA and proteins. Like a tiny locomotive, an enzyme called RNA polymerase runs up and down the DNA copying genetic information.

When it comes to a gene whose protein is needed by the cell, it stops and unwinds the double-stranded DNA, copies one strand and sends it off to machinery to manufacture the new protein. And all is well. But when DNA is damaged by UV radiation or harmful substances, it forms an impenetrable mass that stalls the RNA polymerase, said Smerdon.

Like a boulder on the railroad tracks, the lifeless lump blocks all protein production from that gene. Unless quickly repaired, the cell could die. In healthy people, an enzyme repair crew travels along with the RNA polymerase and instantly rushes in to excise the damage and clear the tracks. This is called transcription-coupled repair, or TCR, an aspect of one of four known DNA repair systems. Smerdon said that even a partial deficiency in any of the repair systems could lead to life-threatening disorders.

Children of the moon

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WSU Researchers Find Crucial Step In DNA Repair