The human set and transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end-joining

Robert Hromas, Justin Wray, Suk Hee Lee, Leah Martinez, Jacqueline Farrington, Lori Kwan Corwin, Heather Ramsey, Jac A. Nickoloff, Elizabeth A. Williamson

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Transposase domain proteins mediate DNA movement from one location in the genome to another in lower organisms. However, in human cells such DNA mobility would be deleterious, and therefore the vast majority of transposase-related sequences in humans are pseudogenes. We recently isolated and characterized a SET and transposase domain protein termed Metnase that promotes DNA double-strand break (DSB) repair by non-homologous end-joining (NHEJ). Both the SET and transposase domain were required for its NHEJ activity. In this study we found that Metnase interacts with DNA Ligase IV, an important component of the classical NHEJ pathway. We investigated whether Metnase had structural requirements of the free DNA ends for NHEJ repair, and found that Metnase assists in joining all types of free DNA ends equally well. Metnase also prevents long deletions from processing of the free DNA ends, and improves the accuracy of NHEJ. Metnase levels correlate with the speed of disappearance of γ-H2Ax sites after ionizing radiation. However, Metnase has little effect on homologous recombination repair of a single DSB. Altogether, these results fit a model where Metnase plays a role in the fate of free DNA ends during NHEJ repair of DSBs.

Original languageEnglish (US)
Pages (from-to)1927-1937
Number of pages11
JournalDNA Repair
Volume7
Issue number12
DOIs
StatePublished - Dec 1 2008

Keywords

  • DNA double-strand break repair
  • DNA Ligase IV
  • Metnase
  • Non-homologous end-joining
  • SET and transposase domain

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hromas, R., Wray, J., Lee, S. H., Martinez, L., Farrington, J., Corwin, L. K., Ramsey, H., Nickoloff, J. A., & Williamson, E. A. (2008). The human set and transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end-joining. DNA Repair, 7(12), 1927-1937. https://doi.org/10.1016/j.dnarep.2008.08.002