English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/24842
Título

Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation

AutorPan-Hammarström, Qiang; Ruiz-Pérez, Victor L. ; Goodship, Judith A.
Fecha de publicación23-ene-2006
EditorRockefeller University Press
CitaciónJournal of Experimental Medicine 203(1): 99-110 (2006)
ResumenClass switch recombination (CSR) and somatic hypermutation (SHM) are mechanistically related processes initiated by activation-induced cytidine deaminase. Here, we have studied the role of ataxia telangiectasia and Rad3-related protein (ATR) in CSR by analyzing the recombinational junctions, resulting from in vivo switching, in cells from patients with mutations in the ATR gene. The proportion of cells that have switched to immunoglobulin (Ig)A and IgG in the peripheral blood seems to be normal in ATR-deficient (ATRD) patients and the recombined S regions show a normal “blunt end-joining,” but impaired end joining with partially complementary (1–3 bp) DNA ends. There was also an increased usage of microhomology at the μ-α switch junctions, but only up to 9 bp, suggesting that the end-joining pathway requiring longer microhomologies (≥10 bp) may be ATR dependent. The SHM pattern in the Ig variable heavy chain genes is altered, with fewer mutations occurring at A and more mutations at T residues and thus a loss of strand bias in targeting A/T pairs within certain hotspots. These data suggest that the role of ATR is partially overlapping with that of ataxia telangiectasia–mutated protein, but that the former is also endowed with unique functional properties in the repair processes during CSR and SHM.
Descripción13 pages, 3 figures, 4 tables.-- et al.
Versión del editorhttp://dx.doi.org/10.1084/jem.20050595
URIhttp://hdl.handle.net/10261/24842
DOI10.1084/jem.20050595
ISSN0022-1007
Aparece en las colecciones: (IIBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Disparate roles.pdf1,31 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.