Non-homologous end joining mediated DNA repair is impaired in the NUP98-HOXD13 mouse model for myelodysplastic syndrome

Leuk Res. 2013 Jan;37(1):112-6. doi: 10.1016/j.leukres.2012.10.012. Epub 2012 Nov 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Checkpoints
  • DNA Breaks, Double-Stranded
  • DNA End-Joining Repair / physiology*
  • Gene Fusion*
  • Homeodomain Proteins / genetics*
  • Mice
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • Nuclear Pore Complex Proteins / genetics*
  • Transcription Factors / genetics*
  • Translocation, Genetic*

Substances

  • Homeodomain Proteins
  • Hoxd13 protein, mouse
  • Nuclear Pore Complex Proteins
  • Transcription Factors
  • nuclear pore complex protein 98