title: Non-homologous end joining mediated DNA repair is impaired in the NUP98-HOXD13 mouse model for myelodysplastic syndrome.
abstract: Chromosomal translocations typically impair cell differentiation and often require secondary mutations for malignant transformation. However, the role of a primary translocation in the development of collaborating mutations is debatable. To delineate the role of leukemic translocation NUP98-HOXD13 (NHD13) in secondary mutagenesis, DNA break and repair mechanisms in stimulated mouse B lymphocytes expressing NHD13 were analyzed. Our results showed significantly reduced expression of non-homologous end joining (NHEJ)-mediated DNA repair genes, DNA Pkcs, DNA ligase4, and Xrcc4 leading to cell cycle arrest at G2/M phase. Our results showed that expression of NHD13 fusion gene resulted in impaired NHEJ-mediated DNA break repair.
authors.affiliation: Laboratory of Molecular Pathology, Center for Molecular Medicine & Infectious Diseases, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Abdul Gafoor
authors.initials: AG
authors.lastname: Puthiyaveetil
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reilly
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Pardee
authors.forename: David L
authors.initials: DL
authors.lastname: Caudell
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair / Q000502:physiology*; D050939:Gene Fusion; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D018398:Homeodomain Proteins; C084118:Hoxd13 protein, mouse; D028861:Nuclear Pore Complex Proteins; D014157:Transcription Factors; C093350:nuclear pore complex protein 98