G4 DNA Binding by LR1 and Its Subunits, Nucleolin and hnRNP D, A Role for G-G pairing in Immunoglobulin Switch Recombination

• Published in: The Journal of biological chemistry 1999-01, Vol.274 (2), p.1066-1071
• Main Authors: Dempsey, Laurie A., Sun, Hui, Hanakahi, L.A., Maizels, Nancy
• Format: Article
• Language: English
• Subjects: Antibodies - immunology; Base Sequence; DNA - metabolism; DNA Primers; DNA-Binding Proteins - metabolism; Heterogeneous-Nuclear Ribonucleoproteins; Immunoglobulin Switch Region - genetics; Nucleolin; Phosphoproteins - immunology; Phosphoproteins - metabolism; Recombinant Proteins - metabolism; Recombination, Genetic; Ribonucleoproteins - immunology; Ribonucleoproteins - metabolism; RNA-Binding Proteins - immunology; RNA-Binding Proteins - metabolism; Transcription Factors - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.2.1066

The immunoglobulin heavy chain switch regions contain multiple runs of guanines on the top (nontemplate) DNA strand. Here we show that LR1, a B cell-specific, duplex DNA binding factor, binds tightly and specifically to synthetic oligonucleotides containing G-G base pairs (KD ≤ 0.25 nm). LR1 also binds to single-stranded G-rich sequences (KD≈ 10 nm). The two subunits of LR1, nucleolin and hnRNP D, bind with high affinity to G4 DNA (KD = 0.4 and 0.5 nm, respectively). LR1 therefore contains two independent G4 DNA binding domains. We propose that LR1 binds with G-G-paired structures that form during the transcription of the S regions that is prerequisite to recombination in vivo. Interactions of donor and acceptor S regions with subunits of the LR1 could then juxtapose the switch regions for recombination.