Detection of a tandem BRCT in Nbs1 and Xrs2 with functional implications in the DNA damage response

Bioinformatics
Emmanuelle BeckerRaphaël Guerois

Abstract

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. 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.

References

Mar 5, 1992·Nature·R LüthyD Eisenberg
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Nov 3, 1998·The EMBO Journal·X ZhangP S Freemont
Mar 10, 2001·Molecular and Cellular Biology·A Desai-MehtaP Concannon
Mar 26, 2002·FEBS Letters·Daniel Durocher, Stephen P Jackson
Apr 23, 2002·Current Biology : CB·Bret R WilliamsJohn H J Petrini
Nov 7, 2002·Current Biology : CB·Junya KobayashiKenshi Komatsu
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Apr 30, 2003·Protein Science : a Publication of the Protein Society·Björn Wallner, Arne Elofsson
Aug 30, 2003·Trends in Cell Biology·John H J Petrini, Travis H Stracker
Sep 2, 2003·EMBO Reports·Michael van den BoschNoel F Lowndes
Oct 25, 2003·Science·Isaac A MankeMichael B Yaffe
Oct 25, 2003·Science·Xiaochun YuJunjie Chen
Feb 13, 2004·Bioinformatics·Michele ClampGeoffrey J Barton
Jul 29, 2004·DNA Repair·Junya KobayashiKenshi Komatsu
Oct 27, 2004·Trends in Biochemical Sciences·J N Mark GloverMegan S Lee
Nov 9, 2004·Bioinformatics·Johannes Söding
Feb 8, 2005·Current Biology : CB·Noel F Lowndes, Geraldine W-L Toh
Mar 1, 2005·The Journal of Biological Chemistry·Jodi R AltChristine M Eischen
Jun 21, 2005·Nature Cell Biology·Simone DifilippantonioAndré Nussenzweig
Jun 28, 2005·Nucleic Acids Research·Johannes SödingAndrei N Lupas
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen

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Citations

Nov 26, 2008·Journal of Applied Genetics·Kamila CzornakKrystyna H Chrzanowska
Nov 13, 2009·Acta Neuropathologica·Elżbieta CiaraKrystyna H Chrzanowska
Oct 29, 2009·Chromosoma·Agnieszka RupnikMuriel Grenon
Aug 7, 2012·Familial Cancer·Kimberly A ZuhlkeKathleen A Cooney
Jan 22, 2011·Nature Reviews. Molecular Cell Biology·Travis H Stracker, John H J Petrini
Aug 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Liming WuJunjie Chen
Mar 1, 2012·Orphanet Journal of Rare Diseases·Krystyna H ChrzanowskaMartin Digweed
Apr 28, 2009·DNA Repair·Sushmita MukherjeeJeff Sekelsky
Jul 5, 2008·DNA Repair·Sylvia SteiningerSimone Moertl
Sep 19, 2007·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Paul S BurgoyneJames M A Turner
Jun 24, 2011·IUBMB Life·Alessandra di MasiPaolo Ascenzi
Apr 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·Chloe GirardAnne M Villeneuve
Dec 7, 2018·Genes·Julyun Oh, Lorraine S Symington
Dec 15, 2019·Cell Death & Disease·Giuseppe BossoGiovanni Cenci
Jul 25, 2009·Journal of Neuro-oncology·Dorota Piekutowska-AbramczukKrystyna H Chrzanowska

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