A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis

Yijie Gao, Yi Sun, Karen M. Frank, Pieter Dikkes, Yuko Fujiwara, Katherine J. Seidl, Jo Ann M. Sekiguchi, Gary A. Rathbun, Wojciech Swat, Jiyang Wang, Roderick T. Bronson, Barbara A. Malynn, Margaret Bryans, Chengming Zhu, Jayanta Chaudhuri, Laurie Davidson, Roger Ferrini, Thomas Stamato, Stuart H. Orkin, Michael E. GreenbergFrederick W. Alt

Research output: Contribution to journalArticlepeer-review

573 Scopus citations


XRCC4 was identified via a complementation cloning method that employed an ionizing radiation (IR)-sensitive hamster cell line. By gene-targeted mutation, we show that XRCC4 deficiency in primary murine cells causes growth defects, premature senescence, IR sensitivity, and inability to support V(D)J recombination. In mice, XRCC4 deficiency causes late embryonic lethality accompanied by defective lymphogenesis and defective neurogenesis manifested by extensive apoptotic death of newly generated postmitotic neuronal cells. We find similar neuronal developmental defects in embryos that lack DNA ligase IV, an XRCC4-associated protein. Our findings demonstrate that differentiating lymphocytes and neurons strictly require the XRCC4 and DNA ligase IV end-joining proteins and point to the general stage of neuronal development in which these proteins are necessary.

Original languageEnglish
Pages (from-to)891-902
Number of pages12
Issue number7
StatePublished - 23 Dec 1998
Externally publishedYes


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