The human set and transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end-joining.
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 gamma-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.
Hromas
Robert
R
Division of Hematology-Oncology, Cancer Research and Treatment Center, Department of Medicine, University of New Mexico Health Science Center, 900 Camino de Salud, Albuquerque, NM 87131, United States.
Wray
Justin
J
Lee
Suk-Hee
SH
Martinez
Leah
L
Farrington
Jacqueline
J
Corwin
Lori Kwan
LK
Ramsey
Heather
H
Nickoloff
Jac A
JA
Williamson
Elizabeth A
EA
D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004249:DNA Damage / Q000502:physiology / Q000528:radiation effects; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology / Q000528:radiation effects; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D056488:Histone Chaperones; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007259:Infrared Rays; D007668:Kidney / Q000378:metabolism; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019895:Transposases / Q000235:genetics / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D056488:Histone Chaperones; D006657:Histones; C000607893:LIG4 protein, human; C513473:SET protein, human; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C510450:SETMAR protein, human; D019895:Transposases; D011088:DNA Ligases; D000072481:DNA Ligase ATP
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