Nucleic Acids Research Advance Access originally published online on April 10, 2007
Nucleic Acids Research 2007 35(8):2682-2694; doi:10.1093/nar/gkm151
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2007, Vol. 35, No. 8 2682-2694
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Biochemical and cellular characteristics of the 3' 
5' exonuclease TREX2
The Department of Molecular Medicine/Institute of Biotechnology, The University of Texas Health Science Center, San Antonio, TX 78245-3207, USA
*To whom correspondence should be addressed. Tel: +508-688-3784; Fax: +508-688-6742; Email: chen0229{at}gmail.com Correspondence may also be addressed to Paul Hasty. Tel: +1-(210) 567-7278; Fax: +(210)567-7247; Email: hastye{at}uthscsa.edu
Received December 19, 2006. Revised February 26, 2007. Accepted February 26, 2007.
TREX2 is an autonomous nonprocessive 3' 
5' exonuclease, suggesting that it maintains genome integrity. To investigate TREX2's biochemical and cellular properties, we show that endogenous TREX2 is expressed widely in mouse tissues and human cell lines. Unexpectedly, endogenous human TREX2 is predominantly expressed as a 30-kDa protein (not 26 kDa, as previously believed), which is likely encoded by longer isoforms (TREX2L1 and/or TREX2L2) that possess similar capacity for self-association, DNA binding and catalytic activity. Site-directed mutagenesis analysis shows that the three functional activities of TREX2 are distinct, yet integrated. Mutation of amino acids putatively important for homodimerization significantly impairs both DNA binding and exonuclease activity, while mutation of amino acids (except R163) in the DNA binding and exonuclease domains affects their corresponding activities. Interestingly, however, DNA-binding domain mutations do not impact catalytic activity, while exonuclease domain mutations diminish DNA binding. To understand TREX2 cellular properties, we find endogenous TREX2 is down regulated during G2/M and nuclear TREX2 displays a punctate staining pattern. Furthermore, TREX2 knockdown reduces cell proliferation. Taken together, our results suggest that TREX2 plays an important function during DNA metabolism and cellular proliferation.
Present address: Ming-Jiu Chen, Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Parra, J. Manils, B. Castellana, A. Vina-Vilaseca, E. Moran-Salvador, N. Vazquez-Villoldo, G. Tarancon, M. Borras, S. Sancho, C. Benito, et al. Increased Susceptibility to Skin Carcinogenesis in TREX2 Knockout Mice Cancer Res., August 15, 2009; 69(16): 6676 - 6684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Hsiao, A. Nakagawa, Z. Shi, S. Mitani, D. Xue, and H. S. Yuan Crystal Structure of CRN-4: Implications for Domain Function in Apoptotic DNA Degradation Mol. Cell. Biol., January 15, 2009; 29(2): 448 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. W. Perrino, U. de Silva, S. Harvey, E. E. Pryor Jr., D. W. Cole, and T. Hollis Cooperative DNA Binding and Communication across the Dimer Interface in the TREX2 3' -> 5'-Exonuclease J. Biol. Chem., August 1, 2008; 283(31): 21441 - 21452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-J. Chen, L. C. Dumitrache, D. Wangsa, S.-M. Ma, H. Padilla-Nash, T. Ried, and P. Hasty Cisplatin Depletes TREX2 and Causes Robertsonian Translocations as Seen in TREX2 Knockout Cells Cancer Res., October 1, 2007; 67(19): 9077 - 9083. [Abstract] [Full Text] [PDF]
|
|