|Home | About | Journals | Submit | Contact Us | Français|
♦ See referenced article, J. Biol. Chem. 2011, 286, J. Biol. Chem. 2010, 286, 40246–40254
The TREX1 exonuclease degrades DNA in the 3′ to 5′ direction to prevent the immune system from improperly reacting against the nucleic acid. The exonuclease is unusual in that it has a dimeric structure. In this Paper of the Week, Fred W. Perrino and co-workers at the Wake Forest School of Medicine (Winston-Salem, North Carolina) explored why a common mutation in TREX1, R114H, leads to the autoimmune disorders Aicardi-Goutières syndrome and systemic lupus erythematosus. Like several other known mutations of the TREX1 enzyme, the R114H mutation causes the enzyme's exonuclease activity to decrease. By studying variations of wild-type and mutant forms of the dimer, the investigators found that Arg-114 is critical for the enzymatic activity of TREX1; the residue reaches across the interface of the dimer to facilitate DNA degradation at the active site of the opposite protomer.