Sequence variants in the 3′ → 5′ deoxyribonuclease TREX2: Identification in a genetic screen and effects on catalysis by the recombinant proteins

Fred W. Perrino, Anna Krol, Scott Harvey, S. Lilly Zheng, David A. Horita, Thomas Hollis, Deborah A. Meyers, William B. Isaacs, Jianfeng Xu

Research output: Contribution to journalArticlepeer-review

Abstract

A genetic analysis of the TREX2 gene identified eleven SNPs: three of these SNPs were missense polymorphisms resulting in the TREX2-S39F, -R137C, and -R156L proteins. A novel bacterial expression system was used to generate these TREX2 proteins for biochemical analysis. Quantification of the activities and kinetic constants of the variant proteins demonstrate that all of these enzymes exhibit robust 3′→5′ deoxyribonuclease activities comparable to TREX2. These results are consistent with the recently determined X-ray structure of the native TREX2 protein (T. Hollis, unpublished results) which indicates that the amino-acid substitutions in the TREX2 variants are positioned in regions of the protein not likely to directly impact on catalytic function. The 3′ nucleotide excision properties of these TREX2 enzymes support the idea that the proteins encoded by the TREX2 SNPs are fully functional 3′→5′ deoxyribonucleases. However, it is possible that diminished cellular function of these TREX2 SNPs is facilitated through alterations it partnering proteins during the processes of DNA replication, repair, or recombination.

Original languageEnglish (US)
Pages (from-to)37-49
Number of pages13
JournalAdvances in Enzyme Regulation
Volume44
Issue number1
DOIs
StatePublished - 2004

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research

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