Structure of a NHEJ Polymerase-Mediated DNA Synaptic Complex

• DOI: 10.1126/science.1145112
• Publication Date: 2007-10-18T20:39:07Z
• Authors: Nigel C. Brissett; Robert S. Pitcher; Raquel Juarez; Angel J. Picher; Andrew J. Green; Timothy R. Dafforn; Gavin C. Fox; Luis Blanco; Aidan J. Doherty
• Keywords: Synapsis; Ku80

Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess minimalist NHEJ apparatus DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure Mycobacterium tuberculosis polymerase domain LigD mediating the synapsis noncomplementary ends revealed variety interactions, including microhomology base pairing, mismatched flipped-out bases, 3' termini forming hairpin-like ends. Biochemical biophysical studies confirmed that polymerase-induced also occurs in solution. We propose this synaptic reflects an intermediate bridging stage process, before processing ligation, with both sequence playing pivotal roles determining sequential order remodeling joining.