Classical and alternative end-joining pathways for repair of lymphocyte-specific and general DNA double-strand breaks.
Classical nonhomologous end joining (C-NHEJ) is one of the two major known pathways for the repair of DNA double-strand breaks (DSBs) in mammalian cells. Our understanding of C-NHEJ has been derived, in significant part, through studies of programmed physiologic DNA DSBs formed during V(D)J recombination in the developing immune system. Studies of immunoglobulin heavy-chain (IgH) class-switch recombination (CSR) also have revealed that there is an "alternative" end-joining process (A-EJ) that can function, relatively robustly, in the repair of DSBs in activated mature B lymphocytes. This A-EJ process has also been implicated in the formation of oncogenic translocations found in lymphoid tumors. In this review, we discuss our current understanding of C-NHEJ and A-EJ in the context of V(D)J recombination, CSR, and the formation of chromosomal translocations.
Howard Hughes Medical Institute, Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, Massachusetts, USA.
Cristian
C
Boboila
Frederick W
FW
Alt
Bjoern
B
Schwer
D000818:Animals; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004260:DNA Repair; D006801:Humans; D017578:Immunoglobulin Class Switching; D008214:Lymphocytes / Q000378:metabolism*; D060152:V(D)J Recombination