Benvenuti nell'Anagrafe della Ricerca d'Ateneo
La valutazione delle attività di ricerca che si svolgono nelle università ha assunto un'importanza rilevante sia per l'intero sistema universitario sia all'interno di ogni singolo ateneo. Roma Tre si è quindi dotata di idonei strumenti informativi in grado di supportare al meglio le azioni di monitoraggio e di valutazione delle attività di ricerca svolte nei propri dipartimentied ha realizzato una Anagrafe della Ricerca di Ateneo.
EnglishNijmegen breakage syndrome (NBS) is a genetic disorder characterized by chromosomal instability and hypersensitivity to ionising radiation. Compound heterozygous 657del5/R215W NBS patients display a clinical phenotype more severe than the majority of NBS patients homozygous for the 657del5 mutation. The NBS1 protein, mutated in NBS patients, contains a FHA/BRCT domain necessary for the DNA-double strand break (DSB) damage response. Recently, a second BRCT domain has been identified, however, its role is still unknown. Here, we demonstrate that the R215W mutation in NBS1 impairs histone gamma-H2AX binding after induction of DNA damage, leading to a delay in DNA-DSB rejoining. Molecular modelling reveals that the 215 residue of NBS1 is located between the two BRCT domains, affecting their relative orientation that appears critical for gamma-H2AX binding. Present data represent the first evidence for the role of NBS1 tandem BRCT domains in gamma-H2AX recognition, and could explain the severe phenotype observed in 657del5/R215W NBS patients. (c) 2008 Elsevier Inc. All rights reserved.
di Masi A, Viganotti M, Polticelli F, Ascenzi P, Tanzarella C, & Antoccia A (2008). The R215W mutation in NBS1 impairs gamma-H2AX binding and affects DNA repair: molecular bases for the severe phenotype of 657del5/R215W Nijmegen breakage syndrome patients RID A-4573-2009. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 369(3), 835-840 [10.1016/j.bbrc.2008.02.129 WC Biochemistry & Molecular Biology; Biophysics].
| Titolo: | The R215W mutation in NBS1 impairs gamma-H2AX binding and affects DNA repair: molecular bases for the severe phenotype of 657del5/R215W Nijmegen breakage syndrome patients RID A-4573-2009 | |
| Autori: | ||
| Data di pubblicazione: | 2008 | |
| Rivista: | ||
| Citazione: | di Masi A, Viganotti M, Polticelli F, Ascenzi P, Tanzarella C, & Antoccia A (2008). The R215W mutation in NBS1 impairs gamma-H2AX binding and affects DNA repair: molecular bases for the severe phenotype of 657del5/R215W Nijmegen breakage syndrome patients RID A-4573-2009. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 369(3), 835-840 [10.1016/j.bbrc.2008.02.129 WC Biochemistry & Molecular Biology; Biophysics]. | |
| Abstract: | Nijmegen breakage syndrome (NBS) is a genetic disorder characterized by chromosomal instability and hypersensitivity to ionising radiation. Compound heterozygous 657del5/R215W NBS patients display a clinical phenotype more severe than the majority of NBS patients homozygous for the 657del5 mutation. The NBS1 protein, mutated in NBS patients, contains a FHA/BRCT domain necessary for the DNA-double strand break (DSB) damage response. Recently, a second BRCT domain has been identified, however, its role is still unknown. Here, we demonstrate that the R215W mutation in NBS1 impairs histone gamma-H2AX binding after induction of DNA damage, leading to a delay in DNA-DSB rejoining. Molecular modelling reveals that the 215 residue of NBS1 is located between the two BRCT domains, affecting their relative orientation that appears critical for gamma-H2AX binding. Present data represent the first evidence for the role of NBS1 tandem BRCT domains in gamma-H2AX recognition, and could explain the severe phenotype observed in 657del5/R215W NBS patients. (c) 2008 Elsevier Inc. All rights reserved. | |
| Handle: | http://hdl.handle.net/11590/153648 | |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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