Bioquímicos descobrem um novo kit de reparos do DNA: mero acaso, fortuita necessidade ou design inteligente???

terça-feira, outubro 04, 2011

Biochemists Identify New Genetic Code Repair Tool

ScienceDaily (Sep. 27, 2011) — Clemson University researchers recently reported finding a new class of DNA repair-makers.

Clemson biochemist Weiguo Cao studies how cells repair damaged DNA. The finding from Cao's lab in the Clemson Biosystems Research Complex in collaboration with computational chemist Brian Dominy appeared in the Sept. 9 issue of The Journal of Biological Chemistry: "A new family of deamination repair enzymes in the uracil DNA glycosylase superfamily by Hyun-Wook Lee, Brian N. Dominy and Weiguo Cao."

"DNA is a string of a long molecule composed of four building blocks: A for adenine, T for thymine, G for guanine and C for cytosine. The heredity of all organisms is determined by the pairing of A with T and G with C," said Cao, a professor in the genetics and biochemistry department.

DNA is constantly assaulted by various stresses. A common type of damage is modification of three out of the four building blocks for genetic code, A, G, C by a chemical process called deamination. The genetic consequence of deamination is that it will change the pairing of the genetic code. For example, the deamination of C (cytosine) will generate U (uracil). Instead of pairing with G as C will do, U pairs with A. In so doing, it changes the genetic program inside the cell and may cause dangerous mutations resulting in disease.

To ensure the integrity of the genetic material, cells are equipped with a "molecular toolkit" for repairing DNA damage. The toolkit is composed of a variety of different molecules -- called enzymes -- that have evolved to repair different types of DNA damage. One of the DNA repair enzymes the Cao lab studies is called uracil DNA glycosylase (UDG). As it's name indicates, it is traditionally known as an enzyme that removes uracil from DNA. Because deamination of C (cytosine) is a very common type of damage found in DNA, UDG has been found in many organisms and researchers have grouped them into five families in the so-called UDG superfamily.

Read more here/Leia mais aqui: Science Daily


New Family of Deamination Repair Enzymes in Uracil-DNA Glycosylase Superfamily*

Hyun-Wook Lee‡, Brian N. Dominy§ and Weiguo Cao‡,1

Author Affiliations

From the ‡Department of Genetics and Biochemistry, South Carolina Experiment Station and
§Department of Chemistry, Clemson University, Clemson, South Carolina 29634

1 To whom correspondence should be addressed: Dept. of Genetics and Biochemistry, South Carolina Experiment Station, Clemson University, Rm. 219 Biosystems Research Complex, 51 New Cherry St., Clemson, SC 29634. Tel.: 864-656-4176; Fax:864-656-0393; E-mail:


DNA glycosylases play a major role in the repair of deaminated DNA damage. Previous investigations identified five families within the uracil-DNA glycosylase (UDG) superfamily. All enzymes within the superfamily studied thus far exhibit uracil-DNA glycosylase activity. Here we identify a new class of DNA glycosylases in the UDG superfamily that lacks UDG activity. Instead, these enzymes act as hypoxanthine-DNA glycosylases in vitro and in vivo. Molecular modeling and structure-guided mutational analysis allowed us to identify a unique catalytic center in this class of DNA glycosylases. Based on unprecedented biochemical properties and phylogenetic analysis, we propose this new class of DNA repair glycosylases that exists in bacteria, archaea, and eukaryotes as family 6 and designate it as the hypoxanthine-DNA glycosylase family. This study demonstrates the structural evolvability that underlies substrate specificity and catalytic flexibility in the evolution of enzymatic function.

DNA Damage, DNA Repair, Enzyme Catalysis, Enzyme Mechanisms, Mutagenesis Mechanisms, DNA Glycosylase, Deamination, Hypoxanthine, Uracil


* This work was supported, in whole or in part, by National Institutes of Health Grant GM090141 (to W. C.). This work was also supported by Cooperative State Research, Education, and Extension Service/United States Department of Agriculture Grant SC-1700274 (Technical Contribution Number 5905), United States Department of Defense Grant W81XWH-10-1-0385 (to W. C.), and National Science Foundation Grant MCB-0953783 (to B. N. D.).

The on-line version of this article (available at contains supplemental Figs. S1–S4.

Received April 9, 2011.
Revision received May 17, 2011.

© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


Professores, pesquisadores e alunos de universidades públicas e privadas com acesso ao site CAPES/Periódicos podem ler gratuitamente este artigo do Journal of Biological Biochemistry e mais 22.440 publicações científicas.



Os autores não explicaram a origem e evolução desta caixa de ferramentas cuja finalidade [Argh, isso é como assassinar Darwin, pois é linguagem teleológica] é consertar erros no DNA.
SPC [Só pra contrariar]: Isso seria melhor descrito pelo referencial teórico do Design Inteligente que preconiza a detecção de sinais de inteligência na natureza.