DNA damage is a constant threat to life. Ultraviolet (UV) radiation from the sun, free radicals produced as byproducts of metabolism, and even the simple wear and tear of cellular processes can all damage DNA. If left unrepaired, this damage can lead to mutations, cell death, and even cancer.
Cells have evolved a number of DNA repair mechanisms to protect themselves from this damage. One of the most important of these mechanisms is called base excision repair (BER). BER repairs damage to individual bases, the building blocks of DNA.
In a paper published in the journal _Nature_, researchers from the University of California, Berkeley, and the Howard Hughes Medical Institute have confirmed the basic mechanism of BER. They found that a protein called poly(ADP-ribose) polymerase-1 (PARP-1) is essential for BER. PARP-1 binds to damaged DNA and recruits other proteins that help to repair the damage.
"This study provides a fundamental understanding of how cells repair DNA damage," said study lead author Dr. Sanjay Kumar. "This knowledge could lead to the development of new therapies for cancer and other diseases that are caused by DNA damage."
The researchers used a combination of biochemical and genetic techniques to study BER in human cells. They found that PARP-1 binds to damaged DNA within seconds of the damage occurring. This binding triggers a cascade of events that leads to the repair of the damage.
The researchers also found that PARP-1 is required for the recruitment of other proteins that are involved in BER. These proteins include DNA polymerase β and ligase IIIα. DNA polymerase β fills in the gap in the DNA strand that is created by the removal of the damaged base, and ligase IIIα seals the gap.
"This study provides a detailed understanding of the molecular mechanisms of BER," said study senior author Dr. Stephen J. Elledge. "This knowledge could lead to the development of new therapies for a variety of diseases that are caused by DNA damage."
DNA damage is a major cause of cancer, and BER is a key mechanism that cells use to repair this damage. By understanding the molecular mechanisms of BER, researchers may be able to develop new drugs that can help to prevent or treat cancer.
