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Bioinformatics Advance Access originally published online on March 7, 2006
Bioinformatics 2006 22(11):1289-1292; doi:10.1093/bioinformatics/btl075
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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Detection of a tandem BRCT in Nbs1 and Xrs2 with functional implications in the DNA damage response

Emmanuelle Becker 1,{dagger}, Vincent Meyer 2,{dagger}, Hocine Madaoui 1 and Raphaël Guerois 1,*

1 Service de Biophysique des Fonctions Membranaires, URA CNRS 2096, Département de Biologie Joliot-Curie CEA Saclay, 91191 Gif-Sur-Yvette, Cedex, France
2 Département d'Etude et d'Ingénierie des Protéines CEA Saclay, 91191 Gif-Sur-Yvette, Cedex, France

*To whom correspondence should be addressed.

Motivation: Human Nbs1 and its homolog Xrs2 in Saccharomyces cerevisiae are part of the conserved MRN complex (MRX in yeast) which plays a crucial role in maintaining genomic stability. NBS1 corresponds to the gene mutated in the Nijmegen breakage syndrome (NBS) known as a radiation hyper-sensitive disease. Despite the conservation and the importance of the MRN complex, the high sequence divergence between Nbs1 and Xrs2 precluded the identification of common domains downstream of the N-terminal Fork-Head Associated (FHA) domain.

Results: Using HMM–HMM profile comparisons and structure modelling, we assessed the existence of a tandem BRCT in both Nbs1 and Xrs2 after the FHA. The structure-based conservation analysis of the tandem BRCT in Nbs1 supports its function as a phosphoserine binding domain. Remarkably, the 5 bp deletion observed in 95% of NBS patients cleaves the tandem at the linker region while preserving the structural integrity of each BRCT domain in the resulting truncated gene products.

Contact: guerois{at}cea.fr

Supplementary information: http://www-spider.cea.fr/Groups/si6661/view.html

Received on January 30, 2006; revised on February 27, 2006; accepted on February 27, 2006

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