V(D)J RECOMBINATION IN KU86-DEFICIENT MICE - DISTINCT EFFECTS ON CODING, SIGNAL, AND HYBRID JOINT FORMATION

Ku, a heterodimer of 70 and 86 kDa subunits, plays a critical but poor ly understood role in V(D)J recombination. Although Ku86-deficient mic e are defective in coding and signal joint formation, rare recombinati on products have been detected by PCR. Here, we report nucleotide sequ ences of 99 junctions from Ku86-deficient mice. Over 90% of the coding joints, but not signal or hybrid joints, exhibit short sequence homol ogies, indicating that homology is required to join coding ends in the absence of Ku86. Our results suggest that Ku86 may normally have dist inct functions in the formation of these different types of junctions. Furthermore, Ku86(-/-) joints are unexpectedly devoid of N-region div ersity, suggesting a novel role for Ku in the addition of N nucleotide s by terminal deoxynucleotidyl transferase.