Wednesday, June 27, 2007

Transcription and DNA Repair

This linked news article, from the National Institutes of Health, Scientists Discover Role of Enzyme in DNA Repair, notes a mechanism involved in DNA repair and the transcription function. From the linked article (in green) (I added the link which helps to explain ataxia telangiectasia):

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.


When DNA is transcribed and damaged DNA is present what happens? Effective repair entails shutting down transcription; specifically interfering with the function of RNA polymerase. Shutting down transcription is accomplished by specified proteins recruited to the site of the DNA damage. Three repair protein factors, ATM, Nbs1 and MDC1, are probably involved in the regulatory shut down function.

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