Nucleolar localization of RAG1 modulates V(D)J recombination activity | Zendy

Ryan M. Brecht | Zendy; Catherine C. Liu | Zendy; Helen A. Beilinson | Zendy; Alexandra Khitun | Zendy; Sarah A. Slavoff | Zendy; David G. Schatz | Zendy

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Nucleolar localization of RAG1 modulates V(D)J recombination activity

Author(s) -

Ryan M. Brecht,

Catherine C. Liu,

Helen A. Beilinson,

Alexandra Khitun,

Sarah A. Slavoff,

David G. Schatz

Publication year - 2020

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.1920021117

Subject(s) - recombination activating gene , rag2 , v(d)j recombination , nucleolus , biology , recombination , microbiology and biotechnology , recombinase , gene , recombination signal sequences , genetics , nucleus

Significance Vertebrate immune systems can respond to many infections and insults. This ability relies on a diverse binding repertoire of antigen receptors. Antigen receptor diversity is created through a process called V(D)J recombination in which arrayed gene segments are shuffled to form functional receptors. This process introduces breaks in chromosomal DNA catalyzed by the RAG1-RAG2 protein complex and requires strict regulation to guard genome integrity. Here we demonstrate a mode of RAG1 regulation by nucleolar sequestration. RAG1’s nucleolar localization is dynamically regulated and is disrupted during a B cell’s transition to a prorecombination state, leading to increased recombination.

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