Endonuclease G, a candidate human enzyme for the initiation of genomic inversion in herpes simplex type 1 virus.

The Journal of Biological Chemistry
Ke-Jung HuangI R Lehman

Abstract

The herpes simplex virus type 1 (HSV-1) a sequence is present as a direct repeat at the two termini of the 152-kilobase viral genome and as an inverted repeat at the junction of the two unique components L and S. During replication, the HSV-1 genome undergoes inversion of L and S, producing an equimolar mixture of the four possible isomers. Isomerization is believed to result from recombination triggered by breakage at the a sequence, a recombinational hot spot. We have identified an enzyme in HeLa cell extracts that preferentially cleaves the a sequence and have purified it to near homogeneity. Microsequencing showed it to be human endonuclease G, an enzyme with a strong preference for G+C-rich sequences. Endonuclease G appears to be the only cellular enzyme that can specifically cleave the a sequence. Endonuclease G also showed the predicted recombination properties in an in vitro recombination assay. Based on these findings, we propose that endonuclease G initiates the a sequence-mediated inversion of the L and S components during HSV-1 DNA replication.

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Citations

Sep 1, 2005·Apoptosis : an International Journal on Programmed Cell Death·M KalinowskaP Widlak
Jan 9, 2009·The Journal of Biological Chemistry·Claudia TemmeElmar Wahle
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May 2, 2009·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Sei Mee YoonEui Jeon Woo
Jun 8, 2012·Journal of Virology·Charlotte MahietSébastien Barradeau
Dec 17, 2004·Molecular and Cellular Biology·Ryan A IrvineMichael R Lieber
Jun 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ke-Jung HuangI Robert Lehman
Aug 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·Amitabh V Nimonkar, Paul E Boehmer
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