Scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Cancer Institute (NCI), and Integrative Bioinformatics Inc. have made an important discovery about the role of an enzyme called ataxia telangiectasia mutated protein (ATM) in the body's ability to repair damaged DNA.
NIAMS and NCI are part of the National Institutes of Health (NIH).
When DNA within a cell is damaged, the cell's protective mechanism must do one of two things: repair the defect or commit suicide, says Rafael Casellas, Ph.D., an investigator in NIAMS Molecular Immunology and Inflammation Branch and leading author of a new paper describing the discovery. But the way in which the cell performs these protective functions has been largely a mystery, says Casellas, whose research is beginning to unravel this mystery.
Casellas research focuses largely on certain genes that are deliberately broken and repaired as part of the immune response. Through a tightly controlled process of breaking and rejoining DNA segments, immune system cells called B lymphocytes are able to produce tens of millions of different types of antibodies to fight almost limitless types of invaders. This process of genetic recombination requires the activity of repair enzymes, which must be able to recognize and repair breaks in tightly wrapped and inaccessible DNA. During immunoglobulin gene recombination, DNA is rendered accessible by the process of transcription, which unzips double-stranded DNA as part of the conversion of genetic information into functional proteins.
While transcription ensures accessibility to DNA lesions, Casellas wondered how it was possible for repair enzymes to do their job if transcription continued once DNA had been damaged.Imagine a piece of DNA as a zipper, he says.The head of the zipper (the transcription complex) will repeatedly go through the two interlocked sides, coming to the broken part, and eventually falling off. One could imagine that this unzipping activity might interfere with the mechanism that is trying to repair the damaged DNA.