Nibrin Protein

Nibrin Protein

Introduction

Nibrin Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">Nibrin (NBS1)</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Nibrin</td></tr>
<tr><td><strong>Gene</strong></td><td><a href="/genes/nbn">NBN (NBS1)</a></td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/O15144">O15144</a></td></tr>
<tr><td><strong>PDB IDs</strong></td><td>1UW4, 2JSS, 2L3X</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>95 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Nucleus, Cytoplasm (in response to DNA damage)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>NBS1 family</td></tr>
</table>
</div>

Overview

Nibrin (also known as NBS1) is a key DNA repair protein that functions as part of the MRN complex (MRE11-RAD50-NBS1). This complex is essential for the recognition and repair of DNA double-strand breaks, maintaining genomic stability.

Structure

Domain Architecture

• N-terminal Region: Contains ATM phosphorylation sites
• Forkhead-Associated (FHA) Domain: Protein-protein interactions
• BRCT Domain: DNA damage response interactions
• C-terminal Region: Mediates interaction with MRE11

...

Nibrin Protein

Introduction

Nibrin Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">Nibrin (NBS1)</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Nibrin</td></tr>
<tr><td><strong>Gene</strong></td><td><a href="/genes/nbn">NBN (NBS1)</a></td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/O15144">O15144</a></td></tr>
<tr><td><strong>PDB IDs</strong></td><td>1UW4, 2JSS, 2L3X</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>95 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Nucleus, Cytoplasm (in response to DNA damage)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>NBS1 family</td></tr>
</table>
</div>

Overview

Nibrin (also known as NBS1) is a key DNA repair protein that functions as part of the MRN complex (MRE11-RAD50-NBS1). This complex is essential for the recognition and repair of DNA double-strand breaks, maintaining genomic stability.

Structure

Domain Architecture

• N-terminal Region: Contains ATM phosphorylation sites
• Forkhead-Associated (FHA) Domain: Protein-protein interactions
• BRCT Domain: DNA damage response interactions
• C-terminal Region: Mediates interaction with MRE11

Key Structural Features

• Phosphorylation at multiple serine/threonine residues
• Forms complex with MRE11 and RAD50
• Rapid recruitment to DNA damage sites
• Contains nuclear localization signals

Post-Translational Modifications

• Phosphorylation: Critical for DNA damage response
• ATM-mediated phosphorylation at Ser343
• Casein kinase 2 (CK2) phosphorylation
• SUMOylation for protein regulation

Normal Function

Role in MRN Complex

• Complex Assembly: Essential for stable MRN complex formation
• DNA Damage Recognition: Primary sensor of DSBs
• Signal Amplification: Recruits and activates ATM kinase

DNA Damage Response

• G1/S Checkpoint: Mediates ATM-Chk2-p53 pathway
• G2/M Checkpoint: Prevents entry into mitosis with unrepaired DNA
• Homologous Recombination: Essential for proper HR execution
• Non-Homologous End Joining: Regulates pathway choice

Cellular Functions

• Telomere maintenance
• Meiotic recombination
• Replication fork stability
• Cell cycle regulation

Role in Disease

Nijmegen Breakage Syndrome (NBS)

Caused by hypomorphic mutations in NBS1:

Pathogenesis:

• Reduced protein function leads to impaired DSB repair
• Genomic instability causes developmental abnormalities
• Increased cancer risk from unresolved DNA damage

Therapeutic Approaches:

• Supportive care for symptoms
• Hematopoietic stem cell transplantation for immunodeficiency
• Cancer surveillance in carriers

Cancer Predisposition

• Heterozygous carriers have 2-4 fold increased breast cancer risk
• Elevated risk of lymphoid malignancies
• Role in sporadic cancers

Neurodegeneration" style="color:#e0e0e0;margin:1.2rem 0 0.5rem;font-size:1rem;font-weight:600;border-bottom:1px solid rgba(255,255,255,0.08);padding-bottom:0.3rem">Neurodegeneration

• Cortical atrophy in NBS patients
• Neurological deterioration in some cases
• Potential role in age-related neurodegeneration

Key Publications

Lee JH, Paull TT (2005). "Direct activation of ATM by DNA requires the full-length NBS1 protein." Science. PMID: 15851777(https://pubmed.ncbi.nlm.nih.gov/15851777/)

Stracker TH, Petrini JH (2008). "The MRE11 complex: at the crossroads of DNA repair and checkpoint signalling." Nat Rev Mol Cell Biol. PMID: 18467000(https://pubmed.ncbi.nlm.nih.gov/18467000/)

Difilippantonio S, et al. (2005). "Role of Nbs1 in DNA damage checkpoint activation." Mol Cell. PMID: 15882743(https://pubmed.ncbi.nlm.nih.gov/15882743/)

See Also

• [NBN Gene](/genes/nbn)
• [Nijmegen Breakage Syndrome](/diseases/nijmegen-breakage-syndrome)
• [DNA Repair Mechanisms](/mechanisms/dna-repair-neurodegeneration)mechanisms/dna-repair-neurodegeneration)
• [MRN Complex](/entities/mrn-complex)
• [MRE11 Protein](/proteins/mre11a-protein)
• [RAD50 Protein](/proteins/rad50-protein)

External Links

• [UniProt: O15144](https://www.uniprot.org/uniprot/O15144)
• [PDB: 1UW4](https://www.rcsb.org/structure/1UW4)
• [GeneReviews: NBS](https://www.ncbi.nlm.nih.gov/books/NBK1156)

Background

The study of Nibrin Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References