The nonamer code for RAG-mediated recombination in vivo.

ABSTRACT: V(D)J recombination, essential for adaptive immunity, is initiated by RAG1/2, which recognizes recombination signal sequences (RSSs) flanking gene segments at antigen receptor loci. RSSs comprise conserved heptamer and nonamer motifs separated by a 12/23-base spacer. While the first three heptamer nucleotides (5'-CAC) are strictly conserved, RSS promiscuity enables RAG "off-target" activity at RSS-like sequences, termed "cryptic RSSs" (cRSSs), contributing to chromosomal deletions and lymphoid tumorigenesis. Notably, the nonamer exhibits substantial sequence variability across physiological RSSs. In addition, many cRSSs lack a discernible nonamer-like sequence, limiting the ability to predict RAG targets based on RSS consensus. Using a high-throughput approach, we characterized here the no

SUBMITTER: Hanout-Chuiko W 

PROVIDER: S-EPMC12711392 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature