4. INTRODUCTION JILA work shows that DNA's backbone does not need to have a small gap, often called a nick, or sport loose ends for the dramatic extension to occur at 65 pN. Scientist discovered how a "chaperone" enzyme plays a key role in cells' ability to tolerate the DNA damage that leads to cancer and other diseases
5. Stretching the Truth: Biophysicists Help Unravel DNA Stretching MysteryScience Daily (Jan. 21, 2011)
6. Stretching the Truth: Biophysicists Help Unravel DNA Stretching Mystery The leading theory is that overstretching introduces so much energy that the DNA melts, with a single strand peeling off from nicks in the backbone or free ends. This model assumes that nicks or ends are essential.
7. Stretching the Truth: Biophysicists Help Unravel DNA Stretching Mystery The JILA team's key advance was a clever geometry that binds a looped end of DNA to a micro-sized bead, while the other end of the DNA has both strands stapled to a surface. Lasers apply force to the bead and measure its position.
8. Stretching the Truth: Biophysicists Help Unravel DNA Stretching Mystery The DNA has freedom to rotate but, crucially, no loose ends. The researchers compared one piece of DNA without nicks or free ends to another piece of DNA they had nicked.
9. Stretching the Truth: Biophysicists Help Unravel DNA Stretching Mystery They found that both molecules overstretched at essentially the same force, indicating the same mechanism is at work in both cases.
13. Chaperone Enzyme Provides New Target for Cancer Treatments In one known example, faulty DNA repair due to Pol eta- deficiency is responsible for the genetic disease xeroderma pigmentosum-variant, which makes patients extremely susceptible to skin cancers caused by exposure to sunlight.
14. Chaperone Enzyme Provides New Target for Cancer Treatments "We found that the mechanism that promotes the 'chaperone' enzyme to recruit Pol eta to sites of DNA damage is managed by another signaling protein termed 'Cdc7' which we know is essential to normal regulation of the cellular lifecycle," said lead author Cyrus Vaziri.
15. Chaperone Enzyme Provides New Target for Cancer Treatments Thus cells employ Cdc7 to ensure accurate DNA repair during the stage of their lifecycle that is most vulnerable to cancer-causing mutations. According to Vaziri, the dual role that Cdc7 plays in the cell lifecycle and DNA repair offers a promising target for potential cancer therapies.
18. MEDICAL UTILITY DNA manages to suddenly extend to almost twice its normal length. The new test structure should support research on DNA elasticity as a standard for tiny forces and help refine studies of how drugs and other substances bind to DNA. drug
