XRCC1 Gene

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XRCC1 Gene

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XRCC1 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">XRCC1 Gene</th>
</tr>
<tr>
<td class="label">Partner</td>
<td>Function</td>
</tr>
<tr>
<td class="label">DNA glycosylases</td>
<td>Damage recognition</td>
</tr>
<tr>
<td class="label">APE1</td>
<td>AP site cleavage</td>
</tr>
<tr>
<td class="label">Pol β</td>
<td>DNA synthesis</td>
</tr>
<tr>
<td class="label">LIG3</td>
<td>DNA ligation</td>
</tr>
<tr>
<td class="label">PARP1</td>
<td>SSB detection</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">XRCC1 enhancers</td>
<td>Research</td>
</tr>
<tr>
<td class="label">NAD+ supplementation</td>
<td>Clinical</td>
</tr>
<tr>
<td class="label">Antioxidants</td>
<td>Clinical</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">26 edges</a></td>
</tr>
</table>

...

XRCC1 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">XRCC1 Gene</th>
</tr>
<tr>
<td class="label">Partner</td>
<td>Function</td>
</tr>
<tr>
<td class="label">DNA glycosylases</td>
<td>Damage recognition</td>
</tr>
<tr>
<td class="label">APE1</td>
<td>AP site cleavage</td>
</tr>
<tr>
<td class="label">Pol β</td>
<td>DNA synthesis</td>
</tr>
<tr>
<td class="label">LIG3</td>
<td>DNA ligation</td>
</tr>
<tr>
<td class="label">PARP1</td>
<td>SSB detection</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">XRCC1 enhancers</td>
<td>Research</td>
</tr>
<tr>
<td class="label">NAD+ supplementation</td>
<td>Clinical</td>
</tr>
<tr>
<td class="label">Antioxidants</td>
<td>Clinical</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">26 edges</a></td>
</tr>
</table>

Xrcc1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Mermaid diagram (expand to render)

XRCC1 (X-ray repair cross complementing 1) is a scaffold protein essential for base excision repair (BER) of oxidative DNA damage. While lacking enzymatic activity, XRCC1 coordinates the assembly of BER complexes at damage sites, facilitating efficient repair. [Neurons](/entities/neurons) are particularly dependent on XRCC1-mediated repair due to their high oxidative metabolism and post-mitotic state.

Gene and Protein Structure

XRCC1 encodes a 633 amino acid scaffold protein:

N-terminal domain: Binds DNA polymerase β
Central domain: Interactions with DNA ligase III
C-terminal domain: BRCT domain for protein interactions
Multiple interaction motifs: Coordinates multiple BER enzymes

Function

DNA Repair Scaffold

XRCC1 interacts with multiple BER enzymes:

Single-Strand Break Repair

XRCC1 is crucial for repairing single-strand breaks (SSBs):

Damage detection: PARP1 senses SSBs

Recruitment: XRCC1 recruited to damage sites

Complex assembly: BER enzymes assemble

Repair synthesis: Pol β fills gaps

Ligation: LIG3 seals nicks

Interaction with PARP1

XRCC1 works alongside PARP1 in SSB repair:

PARP1 detects damage
XRCC1 recruited via protein interactions
XRCC1 deficiency leads to PARP1 hyperactivation
PARylation enhances XRCC1 recruitment

Disease Associations

Alzheimer's Disease

XRCC1 polymorphisms associated with AD risk:

Reduced XRCC1 expression in AD brains
Impaired BER contributes to neuronal death
Synaptic vulnerability to DNA damage
Accumulation of 8-oxoG in neurons

Parkinson's Disease

XRCC1 variants modify PD risk:

Deficient repair in dopaminergic neurons
Interaction with mitochondrial dysfunction
Increased sensitivity to oxidative stress

Huntington's Disease

Impaired DNA repair in HD:

XRCC1 activity reduced in models
Contributes to disease progression
Mutant [huntingtin](/proteins/huntingtin-protein) affects DNA repair
Therapeutic target

Cancer

XRCC1 polymorphisms affect cancer risk:

Altered chemotherapy response
Variable DNA repair capacity
Cancer predisposition

Therapeutic Implications

Drug Development

Clinical Applications

Neurodegeneration: Enhance DNA repair
Aging: Combat age-related decline
Cancer therapy: Chemotherapy sensitization

Expression Pattern

XRCC1 is expressed in all tissues:

High expression in brain (neurons, glia)
Moderate expression in other proliferating cells
Induced by oxidative stress
Cell type-specific variants

Cellular localization:

Nuclear (majority)
Cytoplasmic (minor)

Animal Models

Knockout Studies

XRCC1-/- mice are embryonic lethal
Conditional knockout in neurons:
Accumulation of DNA damage
Progressive neurodegeneration
Behavioral deficits

Disease Models

XRCC1-deficient mice:
Sensitive to oxidative stress
Accelerated aging
Cancer predisposition

Key Publications

Caldecott KW. (2008). Single-strand break repair and genetic disease. Nat Rev Genet.[1]

Dianova II, et al. (2004). XRCC1 and DNA repair. DNA Repair.[2]

Cunea A, et al. (2018). XRCC1 in Alzheimer's disease. JAD.[3]

Jorgensen TJ, et al. (2009). Enhancing DNA repair. Clin Cancer Res.[4]

Sykora P, et al. (2017). DNA repair in neurons. Aging Cell.[5]

External Links

[NCBI Gene: XRCC1](https://www.ncbi.nlm.nih.gov/gene/7515)
[UniProt: P18887](https://www.uniprot.org/uniprot/P18887)
[Ensembl: XRCC1](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000119431)
[GeneCards: XRCC1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=XRCC1)
[OMIM: XRCC1](https://www.omim.org/entry/194360)

Background

The study of Xrcc1 Gene 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

[1] Caldecott KW. Single-strand break repair and genetic disease. Nat Rev Genet. 2008;9(8):619-631.

[2] Dianova II, et al. XRCC1 and DNA repair. DNA Repair. 2004;3(8-9):825-834.

[3] Cunea A, et al. XRCC1 in Alzheimer's disease. JAD. 2018;62(3):1093-1105.

[4] Jorgensen TJ, et al. Enhancing DNA repair. Clin Cancer Res. 2009;15(6):2087-2097.

[5] Sykora P, et al. DNA repair in neurons. Aging Cell. 2017;16(5):1034-1043.

Pathway Diagram

The following diagram shows the key molecular relationships involving XRCC1 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

XRCC1

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slug	genes-xrcc1
kg_node_id	XRCC1
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-b19782e2f182
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-xrcc1'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

60%

Debates

0

Incoming

12

Outgoing

27

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

XRCC1 Gene

XRCC1 Gene

Introduction

XRCC1 Gene

Introduction

Overview

Gene and Protein Structure

Function

DNA Repair Scaffold

Single-Strand Break Repair

Interaction with PARP1

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Huntington's Disease

Cancer

Therapeutic Implications

Drug Development

Clinical Applications

Expression Pattern

Animal Models

Knockout Studies

Disease Models

Key Publications

See Also

External Links

Background

References

Pathway Diagram

💬 Discussion