ArticleJournal of molecular biology2008
Structure of a second BRCT domain identified in the nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- The immediate-early protein 1 of human herpesvirus 6B interacts with NBS1 and inhibits ATM signaling.EMBO reports · 2024Article
- Review
- Phosphopeptide interactions of the Nbs1 N-terminal FHA-BRCT1/2 domains.Scientific reports · 2021Article
- Review
- Yeast XRS2 and human NBN gene: Experimental evidence for homology using codon optimized cDNA.PloS one · 2018Article
- A New BRCT Binding Mode in TopBP1-BLM Helicase Interaction.Structure (London, England : 1993) · 2017Article
- Article
- Archaeal genome guardians give insights into eukaryotic DNA replication and damage response proteins.Archaea (Vancouver, B.C.) · 2014Review
- Structural mechanisms underlying signaling in the cellular response to DNA double strand breaks.Mutation research · 2013Review
- Structural insights into recognition of MDC1 by TopBP1 in DNA replication checkpoint control.Structure (London, England : 1993) · 2013Article
- Charting the landscape of tandem BRCT domain-mediated protein interactions.Science signaling · 2012Article
- Molecular basis for the association of microcephalin (MCPH1) protein with the cell division cycle protein 27 (Cdc27) subunit of the anaphase-promoting complex.The Journal of biological chemistry · 2012Article
- TopBP1 deficiency causes an early embryonic lethality and induces cellular senescence in primary cells.The Journal of biological chemistry · 2011Article
- The MRE11 complex: starting from the ends.Nature reviews. Molecular cell biology · 2011Review
- MDC1: The art of keeping things in focus.Chromosoma · 2010Review
- A divalent FHA/BRCT-binding mechanism couples the MRE11-RAD50-NBS1 complex to damaged chromatin.EMBO reports · 2010Article
- Article
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The Nijmegen breakage syndrome protein Nbs1 is a component of the MRN (Mre11-Rad50-Nbs1) complex, central to the DNA damage response. While Nbs1 is generally believed to encompass a forkhead-associated domain linked to a breast cancer C-terminal (BRCT) domain, to date there is no experimental information on its three-dimensional structure. Through nuclear magnetic resonance (NMR) three-dimensional structure determination, we demonstrate that there is a second BRCT domain (BRCT2) in Nbs1. The domain has the characteristic BRCT topology, but with a long insertion shown to be flexible by NMR relaxation measurements. In the absence of sequence similarity to other proteins, a search for structural analogs of BRCT2 returned the second BRCT domain of the tandem BRCT repeats of cell cycle checkpoint proteins MDC1 (mediator of DNA damage checkpoint protein 1) and BRCA1 (breast cancer protein 1), suggesting that like MDC1 and BRCA1, Nbs1 also possesses tandem BRCT domains with phosphoprotein binding ability. Structure-based single point mutations in human Nbs1 were evaluated in vivo and revealed that BRCT2 is essential for an MDC1-dependent relocalization of Nbs1 to DNA damage sites, most likely through a direct interaction of Nbs1 tandem BRCT domains with phosphorylated MDC1.
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