Open AccessHow mouse RAG recombinase avoids DNA transposition
Author(s) -
X Chen,
Yanxiang Cui,
Huaibin Wang,
Z. Hong Zhou,
Martin Gellert,
Wei Yang
Publication year - 2020
Publication title -
nature structural and molecular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.448
H-Index - 270
eISSN - 1545-9993
pISSN - 1545-9985
DOI - 10.1038/s41594-019-0366-z
Subject(s) - recombinase , transposase , dna , site specific recombination , biology , holliday junction , recombination activating gene , recombination , rag2 , transposition (logic) , recombination signal sequences , genetics , microbiology and biotechnology , transposable element , dna repair , gene , genome , linguistics , philosophy
The RAG1-RAG2 recombinase (RAG) cleaves DNA to initiate V(D)J recombination, but RAG also belongs to the RNH-type transposase family. To learn how RAG-catalyzed transposition is inhibited in developing lymphocytes, we determined the structure of a DNA-strand transfer complex of mouse RAG at 3.1-Å resolution. The target DNA is a T form (T for transpositional target), which contains two >80° kinks towards the minor groove, only 3 bp apart. RAG2, a late evolutionary addition in V(D)J recombination, appears to enforce the sharp kinks and additional inter-segment twisting in target DNA and thus attenuates unwanted transposition. In contrast to strand transfer complexes of genuine transposases, where severe kinks occur at the integration sites of target DNA and thus prevent the reverse reaction, the sharp kink with RAG is 1 bp away from the integration site. As a result, RAG efficiently catalyzes the disintegration reaction that restores the RSS (donor) and target DNA.