Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination.

Abstract:

:The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate V(D)J recombination, the process that assembles the B- and T-lymphocyte antigen receptor genes of jawed vertebrates. RAG1 and RAG2 are thought to have arisen from a transposable element, but the origins of this element are not understood. We show that two ancestral RAG1 proteins, Transib transposase and purple sea urchin RAG1-like, have a latent ability to initiate V(D)J recombination when coexpressed with RAG2 and that in vitro transposition by Transib transposase is stimulated by RAG2. Conversely, we report low levels of V(D)J recombination by RAG1 in the absence of RAG2. Recombination by RAG1 alone differs from canonical V(D)J recombination in having lost the requirement for asymmetric DNA substrates, implicating RAG2 in the origins of the "12/23 rule," a fundamental regulatory feature of the reaction. We propose that evolution of RAG1/RAG2 began with a Transib transposon whose intrinsic recombination activity was enhanced by capture of an ancestral RAG2, allowing for the development of adaptive immunity.

journal_name

Genes Dev

journal_title

Genes & development

authors

Carmona LM,Fugmann SD,Schatz DG

doi

10.1101/gad.278432.116

subject

Has Abstract

pub_date

2016-04-15 00:00:00

pages

909-17

issue

8

eissn

0890-9369

issn

1549-5477

pii

gad.278432.116

journal_volume

30

pub_type

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