The role of the non-homologous end-joining pathway in lymphocyte development

Authors

  • Sean Rooney,

    1. Howard Hughes Medical Institute, The Children's Hospital, The Department of Genetics, Harvard Medical School and The Center for Blood Research, Boston, MA, USA.
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  • Jayanta Chaudhuri,

    1. Howard Hughes Medical Institute, The Children's Hospital, The Department of Genetics, Harvard Medical School and The Center for Blood Research, Boston, MA, USA.
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  • Frederick W. Alt

    Corresponding author
    1. Howard Hughes Medical Institute, The Children's Hospital, The Department of Genetics, Harvard Medical School and The Center for Blood Research, Boston, MA, USA.
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*Fred W. Alt
Children's Hospital
300 Longwood Avenue
New Research Building, 9th Floor
Boston, MA 02115, USA
Tel.: +1 617 919 2539
E-mail: alt@enders.tch.harvard.edu

Abstract

Summary:  One of the most toxic insults a cell can incur is a disruption of its linear DNA in the form of a double-strand break (DSB). Left unrepaired, or repaired improperly, these lesions can result in cell death or neoplastic transformation. Despite these dangers, lymphoid cells purposely introduce DSBs into their genome to maximize the diversity and effector functions of their antigen receptor genes. While the generation of breaks requires distinct lymphoid-specific factors, their resolution requires various ubiquitously expressed DNA-repair proteins, known collectively as the non-homologous end-joining pathway. In this review, we discuss the factors that constitute this pathway as well as the evidence of their involvement in two lymphoid-specific DNA recombination events.

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