. Author manuscript; available in PMC: 2017 Dec 11.

Published in final edited form as: Nat Rev Cancer. 2013 Jun 13;13(7):443–454. doi: 10.1038/nrc3537

Table 1.

Phenotypes of loss-of-function NHEJ mutations Bunting and Nusseznweig, 2013.

NHEJ gene	Mouse knockout phenotype	Patient phenotype
XRCC6 (encoding Ku70)	Viable, SCID, small size, radiosensitivity, thymoma^{48, 49}	None known
XRCC5 (encoding Ku80)	Viable, SCID, small size, radiosensitivity, genomic instability and tumors especially with p53 deletion.^{45, 50–52}	None known
PRKDC (encoding DNA-PKcs)	Viable, SCID, some genomic instability, tumors with p53^53–55	Human hypomorph has SCID, radiosensitivity⁵⁶
DCLRE1C (encoding Artemis)	Viable, SCID, radiosensitivity, genomic instability⁵⁷	Null is SCID, radiosensitivity. Hypomorph is reduction in lymphocytes, instability, lymphoma^{58, 59}
NHEJ1 (encoding XLF)	Mild lymphocytopenia, radio-sensitivity⁶⁰	Cernunnos syndrome; Immunodeficiency, developmental delay, microcephaly, reduced growth, genomic instability⁶¹
XRCC4	Null is lethal with neuronal apoptosis; rescue with p53 is SCID, radiosensitivity, early B lymphoma, genomic instability^{47, 62}	None known
LIG4	Knockout is lethal, neural apoptosis; rescue with p53 gives pro-B lymphoma, radiosensitivity; hypomorph is small, lymphopenic, reduced hematopoietic stem cell function.^{63, 64}	Lig4 syndrome; immunodeficiency, reduced growth, developmental issues, microcephaly, malignancy^{65, 66}

DCLRE1C, DNA cross-link repair 1C; DNA-PKcs, DNA-dependent protein kinase catalytic subunit; LIG4, DNA ligase 4; NHEJ, non-homologous end-joining; NHEJ1, NHEJ factor 1; PRKDC, protein kinase, DNA-activated, catalytic polypeptide; SCID, severe combined immunodeficiency; XLF, XRCC4-like factor; XRCC, X-ray repair cross-complementing protein.