Researchers have discovered that the twisting of molecules of DNA—the body’s blueprint—could play a key role in the sensing and repair of DNA defects, an understanding of which could lead to new insights into disease. Defects in the DNA repair process are associated with several human genetic diseases, including certain cancers, accelerated aging diseases, and some blood disorders. In the new laboratory study using individual DNA molecules, a research team lead by NHLBI’s Andrew Dittmore demonstrated that the twisted (supercoiled) state of cellular DNA creates kinks that prominently expose DNA defects, making them easier targets for detection and repair by cellular proteins. The finding provides a possible mechanism for how proteins that repair DNA can rapidly detect abnormal base pairs (the molecular building blocks of DNA) from among millions of normal intact base pairs. Their study, which appears in Physical Review Letters, was funded by NHLBI.
Physics (American Physical Society): Synopsis: Twisting DNA Locates its Defects