DNA repair could improve cancer therapeutic strategy. « Medicine in the Library

A team of researchers from the College of Veterinary Medicine della Michigan State University made a discovery that could have implications for gene-editing therapeutic strategies, cancer diagnostics and therapies, and other advances in biotechnology.

Researchers have discovered a previously unknown aspect of how double-strand breaks in DNA are repaired.

DNA is surprisingly easy to damage. Damage can be caused by UV exposure and many cancer therapies, including ionizing radiation and some medications. Sometimes, just one thread breaks. Since the DNA is still held together by the second strand, cells can repair the DNA quite easily.

It is more difficult for cells to repair DNA damage when both strands are broken. Double-strand breaks can also be more difficult to repair if DNA-damaging agents cause chemical changes to the ends of the DNA. The damaged ends of the DNA are often referred to as the “dirty” ends.

DNA-PK can help repair double-strand breaks in DNA in two ways. For breaks with missing information, it can target enzymes that can fill in the missing nucleotides, a kind of needle and thread that stitches DNA back together. For the “dirty” ends, DNA-PK recruits enzymes that can cut the damaged DNA so that the ends can be rejoined.

Two distinct long-range synaptic complexes promote different aspects of end processing prior to repair of DNA breaks by non-homologous end joining.
Christopher J. Buehl, Noah J. Goff, Steven W. Hardwick, Martin Gellert, Tom L. Blundell, Wei Yang, Amanda K. Chaplin, Katheryn Meek.
Molecular Cell2023; 83 (5): 698 DOI: 10.1016/j.molcel.2023.01.012