title: Programmed DNA breaks in lymphoid cells: repair mechanisms and consequences in human disease.
abstract: In recent years, several novel congenital human disorders have been described with defects in lymphoid B-cell and T-cell functions that arise due to mutations in known and/or novel components of DNA repair and damage response pathways. Examples include impaired DNA double-strand break repair, as well as compromised DNA damage-induced signal transduction, including phosphorylation and ubiquitination. These disorders reinforce the importance of genome stability pathways in the development of lymphoid cells in humans. Furthermore, these conditions inform our knowledge of the biology of the mechanisms of genome stability and in some cases may provide potential routes to help exploit these pathways therapeutically. Here we review the mechanisms that repair programmed DNA lesions that occur during B-cell and T-cell development, as well as human diseases that arise through defects in these pathways.
authors.affiliation: CeMM Research Centre for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Jana
authors.initials: J
authors.lastname: Prochazkova
authors.affiliation: CeMM Research Centre for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Joanna I
authors.initials: JI
authors.lastname: Loizou
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
keywords: DNA repair; V(D)J recombination; cancer; class switch recombination; immunodeficiency; non-homologous end-joining