A histidine in the beta-CASP domain of Artemis is critical for its full in vitro and in vivo functions

作者：de Villartay Jean Pierre^*; Shimazaki Noriko; Charbonnier Jean Baptiste; Fischer Alain; Mornon Jean Paul; Lieber Michael R; Callebaut Isabelle

来源：DNA Repair, 2009, 8(2): 202-208.

DOI：10.1016/j.dnarep.2008.10.010

• Artemis
• HCA
• Metallo-beta-lactamase
• NHEJ
• SCID

Artemis is a key factor of the nonhomologous end-joining (NHEJ) pathway, which is critical for DNA double-strand break (DSB) repair in eukaryotic cells. It belongs to the beta-CASP family of nucleases, forming a distinct group within the metallo-beta-lactamase superfamily. Proteins of this group are specific for nucleic acids and contain an original domain, the beta-CASP domain. which serves as a cap covering the active site displayed by the metallo-beta-lactamase domain. Here, we have identified in the highly divergent sequences of the beta-CASP domains from DNA-specific nucleases two conserved residues (Artemis E213 and H254), which are not present in RNA-specific enzymes, and shown that H254 plays a key role in the Artemis function, as it is critical for its full activity in vitro. Moreover, inherited mutation of H254 results in radiosensitive severe combined immune deficiency (RS-SCID) in humans. This residue might play a key role in specificity towards DNA, if not directly in zinc binding.

• 出版日期2009-2-1
• 单位中国地震局