Description
Title: End joining of the DNA: G0-ing to the Core
Abstract: To effectively rejoin newly formed pairs of double-stranded DNA ends, humans have evolved a variety of DNA double-strand break (DSB) repair pathways (DSEs). Non-homologous end joining (NHEJ) and alternative end joining (A-EJ) support the covalent rejoining of DSEs in G0/G1-phase cells. While NHEJ is frequently used and works closely with the DNA damage response (DDR) to support pairing of DSEs, A-interaction EJ’s with DDR factors when NHEJ is not present is much less well understood. The V(D)J recombination of antigen receptor genes is finished by non-cycling lymphocyte progenitor cells using NHEJ. This process is started by the RAG1/2 endonuclease, which holds its pair of targeted DSBs in a synapse until each specific pair of DSEs is transferred to the NHEJ DSB sensor complex, Ku. The absence of Ku permits A-EJ to access RAG1/2 DSEs with random pairing, much like designer endonuclease DSBs, and complete their repair. Here, we discuss new and established ideas about NHEJ vs. A-EJ and the choice of RAG2-mediated repair pathway by describing recent insights into the major phases of DSB end joining with a focus on synapsis and tethering mechanisms.
Keywords: NHEJ; A-EJ; DSB repair; non-cycling; end joining; synapse; tethering; V(D)J recombination; translocation; functional redundancy
Paper Quality: SCOPUS / Web of Science Level Research Paper
Subject: Biomolecules
Writer Experience: 20+ Years
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