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DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency

Lookup NU author(s): Professor Andrew GenneryORCiD

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Abstract

DNA ligase IV functions in DNA nonhomologous end-joining and V(D)J recombination. Four patients with features including immunodeficiency and developmental and growth delay were found to have mutations in the gene encoding DNA ligase IV (LIG4). Their clinical phenotype closely resembles the DNA damage response disorder, Nijmegen breakage syndrome (NBS). Some of the mutations identified in the patients directly disrupt the ligase domain while others impair the interaction between DNA ligase IV and Xrcc-4. Cell lines from the patients show pronounced radiosensitivity. Unlike NBS cell lines, they show normal cell cycle checkpoint responses but impaired DNA double-strand break rejoining. An unexpected V(D)J recombination phenotype is observed involving a small decrease in rejoining frequency coupled with elevated imprecision at signal junctions.

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Author(s): O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P

Publication type: Article

Publication status: Published

Journal: Molecular Cell

Year: 2001

Volume: 8

Issue: 6

Pages: 1175-1185

Print publication date: 01/12/2001

Online publication date: 05/01/2002

Acceptance date: 01/10/2001

ISSN (print): 1097-2765

ISSN (electronic): 1097-4164

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/S1097-2765(01)00408-7

DOI: 10.1016/S1097-2765(01)00408-7

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