MSGID: 1:317/3 640177e0   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    DNA repair discovery could improve biotechnology    
      
     Date:   
         March 2, 2023   
     Source:   
         Michigan State University   
     Summary:   
         A team of researchers has made a discovery that may have   
         implications for therapeutic gene editing strategies, cancer   
         diagnostics and therapies and other advancements in biotechnology.   
      
      
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   FULL STORY   
   ==========================================================================   
   A team of researchers from Michigan State University's College of   
   Veterinary Medicine has made a discovery that may have implications for   
   therapeutic gene editing strategies, cancer diagnostics and therapies   
   and other advancements in biotechnology.   
      
      
   ==========================================================================   
   Kathy Meek, a professor in the College of Veterinary Medicine, and   
   collaborators at Cambridge University and the National Institutes   
   of Health have uncovered a previously unknown aspect of how DNA   
   double-stranded breaks are repaired.   
      
   A large protein kinase called DNA-PK starts the DNA repair process; in   
   their new report, two distinct DNA-PK protein complexes are characterized,   
   each of which has a specific role in DNA repair that cannot be assumed   
   by the other.   
      
   "It still gives me chills," says Meek. "I don't think anyone would have   
   predicted this."  Meek's findings are published in Molecular Cell,a   
   high-impact journal that covers core cellular processes like DNA repair.   
      
   How DNA double-stranded breaks are repaired DNA, the blueprint of   
   life, is shaped like a helix; however, DNA is surprisingly easy to   
   damage. Ultraviolet light, for example, and many cancer therapies   
   including ionizing radiation and other specific drugs can all cause damage   
   to DNA. Sometimes, only one of the two strands break. Because the DNA is   
   still held together by the second strand, cells can repair the DNA fairly   
   easily -- the cells just copy the information from the second strand.   
      
   It is more difficult for cells to repair DNA damage when both strands   
   are broken. Information in the form of nucleotides can be lost and   
   must be added back in before the DNA ends are rejoined. If a cell has   
   multiple DNA double- stranded breaks, the DNA ends can be joined with   
   the wrong partner. This type of mistake is often associated with many   
   types of cancers.   
      
   Double-stranded breaks also can be more difficult to repair if   
   DNA-damaging agents cause chemical modifications at the DNA ends. Damaged   
   DNA ends are often referred to as "dirty" ends.   
      
   DNA-PK can help repair DNA double-stranded breaks in one of two ways. For   
   breaks with missing information, it can target enzymes that can fill in   
   missing nucleotides -- sort of like a needle and thread stitching the   
   DNA back together. For "dirty" ends, DNA-PK recruits enzymes that can   
   cut off the damaged DNA so that the ends can be rejoined.   
      
   This much was already known, but a key question remained unanswered in   
   the scientific literature -- until now: how does DNA-PK know whether to   
   fill in or cut off ends at a double-stranded break?  Discovery of two   
   DNA-PK complexes: Fill in and cut off Meek's team and their collaborators   
   previously published structural studies that revealed two different   
   DNA-PK complexes, called dimers. While many molecular geneticists already   
   suspected that DNA-PK helps hold DNA ends together during the rejoining   
   process, many wondered why there would be two dimers, instead of just one.   
      
   In their new study, Meek and her collaborators discovered that the two   
   distinct DNA-PK dimers have different functions; one complex recruits   
   enzymes that fill in lost information, while the other activates cutting   
   enzymes that remove "dirty" ends. The team also discovered that repair   
   efficacy depends on equilibrium between the two dimers.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Genes # Human_Biology # Forensics   
             o Matter_&_Energy   
                   # Organic_Chemistry # Biometric # Microarrays   
             o Computers_&_Math   
                   # Computational_Biology # Encryption #   
                   Information_Technology   
       * RELATED_TERMS   
             o Drug_discovery o Gene_therapy o Cervical_cancer o   
             BRCA1 o Breast_cancer o Biopharmaceutical o Stem_cell o   
             Energy_(healing_or_psychic_or_spiritual)   
      
   ==========================================================================   
   Story Source: Materials provided by Michigan_State_University. Original   
   written by Emily Lenhard. Note: Content may be edited for style and   
   length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Christopher J. Buehl, Noah J. Goff, Steven W. Hardwick, Martin   
      Gellert,   
         Tom L. Blundell, Wei Yang, Amanda K. Chaplin, Katheryn Meek. Two   
         distinct long-range synaptic complexes promote different   
         aspects of end processing prior to repair of DNA breaks by   
         non-homologous end joining. Molecular Cell, 2023; 83 (5): 698 DOI:   
         10.1016/j.molcel.2023.01.012   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/03/230302114017.htm   
      
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