The metallo-β-lactamase/β-CASP domain of artemis constitutes the catalytic core for V(D)J recombination

被引：75

作者：

Poinsignon, C

Moshous, D

Callebaut, I

de Chasseval, R

Villey, I

de Villartay, JP

机构：

[1] Hop Necker Enfants Malad, INSERM, U429, F-75015 Paris, France

[2] Univ Paris 06, CNRS, UMR7590, F-75005 Paris, France

[3] Univ Paris 07, CNRS, UMR7590, F-75005 Paris, France

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2004年 / 199卷 / 03期

关键词：

Artemis; metallo-beta-lactamases; beta-CASP; V(D)J recombination; DNA repair;

D O I：

10.1084/jem.20031142

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The V(D)J recombination/DNA repair factor Artemis belongs to the metallo-beta-lactamase (beta-Lact) superfamily of enzymes. Three regions can be defined within the Artemis protein sequence: (a) the beta-Lact homology domain, to which is appended (b) the beta-CASP region, specific of members of the beta-Lact superfamily acting on nucleic acids, and (c) the COOH-terminal domain. Using in vitro mutagenesis, here we show that the association of the beta-Lact and the eta-CASP regions suffices for in vivo V(D)J recombination of chromosome-integrated substrates. Single amino acid mutants point to critical catalytic residues for V(D)J recombination activity. The results presented here define the beta-Lact/beta-CASP domain of Artemis as the minimal core catalytic domain needed for V(D)J recombination and suggest that Artemis uses one or two Zn(II) ions to exert its catalytic activity, like bacterial class B beta-Lact enzymes hydrolyzing beta-lactam compounds.

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页码：315 / 321

页数：7

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