Table 1.

Effects on V(D)J recombination in DNA-PKcs mutants

Mutants		Mutation*	DNA-PKcs†			V(D)J‡		sj fidelity, %	Refs.
			Level	Binding	Activity	cj	sj
Cell lines§
SCGR11	SCID(m)	pt4045	—	—	—	Defective	Normal	80	9, 28
fibrobl	SCID(m)	pt4045	ND	ND	ND	Defective	Normal	80	27
pre-B	SCID(m)	pt4045	ND	ND	ND	Defective	Reduced	50	19
SX-9	MC(m)	L3192P	+	+	—	Defective	10X↓¶	12	45, 51
irs-20	CHO	E4124K	++	+	—	Defective	8X↓	75	46, 51, 52
MO59J	MG(h)	nd	—	ND	—	Defective	Normal	95	35, 53
V3	CHO	pt4024	—	—	—	Defective	2-10X↓	47–80	8, 9, 27, 46, 51
DNA-PKcsN/N	ES(m)	null	—	ND	—	Defective	2.5X↓	100	40
XR-C1	CHO	nd	—	ND	—	Defective	60X↓	—	54
Animals
SCID	equ	pt3160	—	ND	—	Defective	Defective	—	55, 56
SCID	mur	pt4045	+	+	±‖	Defective	10X↓	∼50	11–14, 38, this work
DNA-PKcsN/N	mur	null	—	ND	—	Defective	10X↓	∼100	40
SLIP	mur	null	—	ND	ND	Defective	10X↓	∼50	37, this work

ND, not done. 

^*pt, premature termination; amino acid substitutions indicated by amino acid number preceded by wild-type amino acid (single-letter abbreviation) followed by substitution. The irs-20 mutation also was reported as E4120K (46). Note that the kinase domain is between amino acids 3719 and 4127. 

^†Level, relative DNA-PKcs protein levels compared with wild type at +++; Binding, DNA-PK binding to DNA; Activity, DNA-PKcs activity. 

^‡cj, coding joint; sj, signal joint. Fold reductions are included as reported or calculated by us from reported data. Defective, low to undetectable; normal, wild-type levels; reduced, less than normal, but not as severe as defective. 

^§(m), murine; (h), human; MC, mammary carcinoma; MG, malignant glioma; CHO, Chinese hamster ovary; ES, embryonic stem cell. 

^¶Although SX9 was reported to be defective in both coding and signal joint formation, the data show that the signal joint defect is only 10-fold below wild type. 

^‖SCID murine embryonic fibroblasts showed low levels of DNA-PK activity (14), whereas SCID thymocytes showed no detectable activity (12).