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Switch Tandem Repeats Influence the Choice of the Alternative End-Joining Pathway in Immunoglobulin Class Switch Recombination.
Oudinet, Chloé; Zhang, Xuefei; Puget, Nadine; Kyritsis, Nia; Leduc, Claire; Braikia, Fatima-Zohra; Dauba, Audrey; Alt, Frederick W; Khamlichi, Ahmed Amine.
Afiliación
  • Oudinet C; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, Université Paul Sabatier, Toulouse, France.
  • Zhang X; Program in Cellular and Molecular Medicine, Howard Hughes Medical Institute, Department of Genetics, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
  • Puget N; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, Université Paul Sabatier, Toulouse, France.
  • Kyritsis N; Program in Cellular and Molecular Medicine, Howard Hughes Medical Institute, Department of Genetics, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
  • Leduc C; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, Université Paul Sabatier, Toulouse, France.
  • Braikia FZ; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, Université Paul Sabatier, Toulouse, France.
  • Dauba A; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, Université Paul Sabatier, Toulouse, France.
  • Alt FW; Program in Cellular and Molecular Medicine, Howard Hughes Medical Institute, Department of Genetics, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
  • Khamlichi AA; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, Université Paul Sabatier, Toulouse, France.
Front Immunol ; 13: 870933, 2022.
Article en En | MEDLINE | ID: mdl-35651614
Immunoglobulin class switch recombination (CSR) plays an important role in humoral imm\une responses by changing the effector functions of antibodies. CSR occurs between highly repetitive switch (S) sequences located upstream of immunoglobulin constant gene exons. Switch sequences differ in size, the nature of their repeats, and the density of the motifs targeted by the activation-induced cytidine deaminase (AID), the enzyme that initiates CSR. CSR involves double-strand breaks (DSBs) at the universal Sµ donor region and one of the acceptor S regions. The DSBs ends are fused by the classical non-homologous end-joining (C-NHEJ) and the alternative-NHEJ (A-NHEJ) pathways. Of the two pathways, the A-NHEJ displays a bias towards longer junctional micro-homologies (MHs). The Sµ region displays features that distinguish it from other S regions, but the molecular basis of Sµ specificity is ill-understood. We used a mouse line in which the downstream Sγ3 region was put under the control of the Eµ enhancer, which regulates Sµ, and analyzed its recombination activity by CSR-HTGTS. Here, we show that provision of Eµ enhancer to Sγ3 is sufficient to confer the recombinational features of Sµ to Sγ3, including efficient AID recruitment, enhanced internal deletions and robust donor function in CSR. Moreover, junctions involving Sγ3 display a bias for longer MH irrespective of sequence homology with switch acceptor sites. The data suggest that the propensity for increased MH usage is an intrinsic property of Sγ3 sequence, and that the tandem repeats of the donor site influence the choice of the A-NHEJ.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cambio de Clase de Inmunoglobulina / Reparación del ADN por Unión de Extremidades Límite: Animals Idioma: En Revista: Front Immunol Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cambio de Clase de Inmunoglobulina / Reparación del ADN por Unión de Extremidades Límite: Animals Idioma: En Revista: Front Immunol Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza