TY - JOUR
T1 - The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations
AU - Wray, Justin
AU - Williamson, Elizabeth A.
AU - Chester, Sean
AU - Farrington, Jacqueline
AU - Sterk, Rosa
AU - Weinstock, David M.
AU - Jasin, Maria
AU - Lee, Suk Hee
AU - Nickoloff, Jac A.
AU - Hromas, Robert
N1 - Funding Information:
S.-H.L. was supported by National Institutes of Health (NIH) grant CA92111 and the U.S. Army ( DAMD17-00-1-0295 ), B.D.B. was supported by an NIH predoctoral training grant (T32 DK0075-20) , the Walther Cancer Institute, and the IU Simon Cancer Center, J.A.N. was supported by NIH grant CA100862 , and R.H. was supported by NIH grants HL093606 , CA139429 , and CA140442 .
PY - 2010/7
Y1 - 2010/7
N2 - Chromosomal translocations are common in leukemia, but little is known about their mechanism. Metnase (also termed SETMAR) is a fusion of a histone methylase and transposase protein that arose specifically in primates. Transposases were thought to be extinct in primates because they would mediate deleterious DNA movement. In primates, Metnase interacts with DNA Ligase IV (Lig IV) and promotes nonhomologous end-joining (NHEJ) DNA repair. We show here that the primate-specific protein Metnase can also enhance NHEJ in murine cells and can also interact with murine Lig IV, indicating that it integrated into the preexisting NHEJ pathway after its development in primates. Significantly, expressing Metnase in murine cells significantly reduces chromosomal translocations. We propose that the fusion of the histone methylase SET domain and the transposase domain in the anthropoid lineage to form primate Metnase promotes accurate intrachromosomal NHEJ and thereby suppresses interchromosomal translocations. Metnase may have been selected for because it has a function opposing transposases and may thus play a key role in suppressing translocations that underlie oncogenicity.
AB - Chromosomal translocations are common in leukemia, but little is known about their mechanism. Metnase (also termed SETMAR) is a fusion of a histone methylase and transposase protein that arose specifically in primates. Transposases were thought to be extinct in primates because they would mediate deleterious DNA movement. In primates, Metnase interacts with DNA Ligase IV (Lig IV) and promotes nonhomologous end-joining (NHEJ) DNA repair. We show here that the primate-specific protein Metnase can also enhance NHEJ in murine cells and can also interact with murine Lig IV, indicating that it integrated into the preexisting NHEJ pathway after its development in primates. Significantly, expressing Metnase in murine cells significantly reduces chromosomal translocations. We propose that the fusion of the histone methylase SET domain and the transposase domain in the anthropoid lineage to form primate Metnase promotes accurate intrachromosomal NHEJ and thereby suppresses interchromosomal translocations. Metnase may have been selected for because it has a function opposing transposases and may thus play a key role in suppressing translocations that underlie oncogenicity.
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U2 - 10.1016/j.cancergencyto.2010.04.011
DO - 10.1016/j.cancergencyto.2010.04.011
M3 - Article
C2 - 20620605
AN - SCOPUS:77953743403
SN - 0165-4608
VL - 200
SP - 184
EP - 190
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
IS - 2
ER -