The structure-specific nicking of small heteroduplexes by the RAG complex

Implications for lymphoid chromosomal translocations

Sathees C. Raghavan, Jiafeng Gu, Patrick Swanson, Michael R. Lieber

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

During V(D)J recombination, the RAG complex binds at recombination signal sequences and creates double-strand breaks. In addition to this sequence-specific recognition of the RSS, the RAG complex has been shown to be a structure-specific nuclease, cleaving 3′ overhangs and 3′ flaps, and, more recently, 10 nucleotides (nt) bubble (heteroduplex) structures. Here, we assess the smallest size heteroduplex that core and full-length RAGs can cleave. We also test whether bubbles adjacent to a partial RSS are nicked any differently or any more efficiently than bubbles that are surrounded by random sequence. These points are important in considering what types and what size of non-B DNA structure that the RAG complex can nick, and this helps assess the role of the RAG complex in mediating lymphoid chromosomal translocations. We find that the smallest bubble nicked by the RAG complex is 3 nt, and proximity to a partial or full RSS sequence does not affect the nicking by RAGs. RAG nicking efficiency increases with the size of the heteroduplex and is only about two-fold less efficient than an RSS when the bubble is 6 nt. We consider these findings in the context of RAG nicking at non-B DNA structures in lymphoid chromosomal translocations.

Original languageEnglish
Pages (from-to)751-759
Number of pages9
JournalDNA Repair
Volume6
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

RSS
Genetic Translocation
Nucleotides
3'-nucleotidase
V(D)J Recombination
DNA
Protein Sorting Signals
Flaps
Genetic Recombination

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

The structure-specific nicking of small heteroduplexes by the RAG complex : Implications for lymphoid chromosomal translocations. / Raghavan, Sathees C.; Gu, Jiafeng; Swanson, Patrick; Lieber, Michael R.

In: DNA Repair, Vol. 6, No. 6, 01.06.2007, p. 751-759.

Research output: Contribution to journalArticle

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