RAD54 Gene

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RAD54 Gene

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RAD54 Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RAD54 Gene</th>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">RAD51</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">RAD51B</td>
<td>Complex formation</td>
</tr>
<tr>
<td class="label">RAD51C</td>
<td>Complex formation</td>
</tr>
<tr>
<td class="label">DMC1</td>
<td>Functional interaction</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">13 edges</a></td>
</tr>
</table>

...

RAD54 Gene

Overview

Mermaid diagram (expand to render)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RAD54 Gene</th>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">RAD51</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">RAD51B</td>
<td>Complex formation</td>
</tr>
<tr>
<td class="label">RAD51C</td>
<td>Complex formation</td>
</tr>
<tr>
<td class="label">DMC1</td>
<td>Functional interaction</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">13 edges</a></td>
</tr>
</table>

RAD54 (RAD54 homolog) is a gene that encodes a DNA-dependent ATPase protein essential for homologous recombination and DNA repair. The protein plays crucial roles in repairing DNA double-strand breaks (DSBs), maintaining genome stability, and regulating chromatin dynamics. RAD54 is a member of the SWI2/SNF2 family of chromatin remodelers and functions as a key accessory factor in the RAD51-mediated homologous recombination pathway. [@li2002]

The RAD54 gene is located on chromosome 1p36.11 and encodes a 754-amino acid protein that possesses both ATP-dependent chromatin remodeling activity and DNA strand exchange stimulation functions. This dual functionality positions RAD54 as a central regulator of DNA repair and genome stability. [@tanaka2000]

Gene Structure and Organization

Genomic Location

Chromosome: 1p36.11
Gene ID: 8438
Genomic position: Approximately 23,900,000-23,950,000 (GRCh38)
Strand: Minus/antisense strand
Gene family: SWI2/SNF2 family

Gene Structure

The RAD54 gene consists of multiple exons: [@miyazaki2004]

Exon count: 21 exons distributed across the genomic locus
Promoter elements: Contains promoter and enhancer regulatory elements
Transcriptional regulation: Responsive to DNA damage and cell cycle signals

Protein Structure

The RAD54 protein has the following structural features: [@udayakumar2003]

Primary Structure

Length: 754 amino acids
Molecular weight: ~83 kDa
Isoelectric point: ~9.0 (basic protein)

Domain Organization

SWI2/SNF2 ATPase Domain

Location: Central region of the protein
Function: ATP-dependent DNA translocase activity
Motifs: Contains the characteristic DEAD-box helicase motifs

HMG-box-like Domain

Location: C-terminal region
Function: DNA bending and protein-protein interactions
DNA binding: Non-sequence specific DNA interaction

Additional Domains

Q-rich region: Glutamine-rich transcriptional activation domain
Rad51 interaction domain: N-terminal region for protein interactions

Biological Functions

DNA Double-Strand Break Repair

RAD54 plays essential roles in homologous recombination: [@barone2010]

RAD51 Stimulation

Filament stabilization: RAD54 stabilizes RAD51-ssDNA filaments
Strand exchange: Stimulates RAD51-mediated DNA strand exchange
Homology search: Facilitates the homology search process
D-loop formation: Promotes D-loop formation

Chromatin Remodeling

Nucleosome eviction: ATP-dependent nucleosome removal
Chromatin accessibility: Opens chromatin for repair factors
Histone modification: Modifies histone tails during repair

DNA Damage Response

RAD54 participates in the DNA damage response: [@esguerra2018]

Signalling

ATM/ATR activation: Responds to DNA damage signalling
Checkpoint activation: Contributes to cell cycle arrest
Damage recognition: Helps locate DNA lesions

Repair

Alternative pathways: Functions in backup DSB repair
Backup pathways: Compensates for BRCA1/2 deficiency
Error-free repair: Promotes error-free homologous recombination

Transcriptional Regulation

RAD54 has transcription-related functions: [@krejci2012]

Chromatin Remodeling

Transcriptional activation: Remodels chromatin at target genes
Co-activator function: Works with transcriptional co-activators
Gene regulation: Affects expression of various genes

Stress Response Genes

DNA damage response genes: Regulates damage response gene expression
Cell cycle genes: Modulates cell cycle regulatory genes
Apoptosis genes: Can influence apoptotic gene expression

Role in Neurobiology

DNA Repair in Neurons

Neurons rely on DNA repair mechanisms: [@sanjana2012]

Post-mitotic cells: Cannot use recombination for division
Oxidative stress: High oxidative damage in neurons
Base excision repair: Important for single-strand damage
Nucleotide excision repair: UV-induced damage repair

Neurological Disorders

RAD54 has been implicated in neurological conditions: [@zhang2015]

Neurodegeneration

DNA damage accumulation: Defects may lead to damage accumulation
Aging: Age-related decline in DNA repair
Neurodegenerative diseases: Potential roles in AD, PD

Cancer Predisposition

Lynch syndrome connections: Overlapping with mismatch repair
Brain tumors: Some brain tumor associations
Therapeutic implications: DNA repair as therapeutic target

Brain Development

RAD54 may play roles in neurodevelopment: [@liu2014]

Proliferation: Required for rapid cell division
Differentiation: May affect neural differentiation
Genomic stability: Maintains genome integrity in neural precursors

Cancer Biology

Tumor Suppressor Function

RAD54 has tumor suppressor properties: [@cappadocia2020]

DNA Repair Functions

Genome stability: Maintains genomic integrity
Mutagenesis prevention: Prevents mutation accumulation
Chromosomal stability: Prevents chromosome breaks

Cancer Suppression

Tumor suppression: Loss promotes tumorigenesis
Interaction with BRCA pathway: Works with BRCA1/2
Synthetic lethality: Potential therapeutic target

Cancer Associations

RAD54 alterations in cancer: [@hentschel2016]

Reduced expression: Often downregulated in tumors
Mutation frequency: Variable across cancer types
Prognostic value: In some cancer types

Therapeutic Implications

RAD54 as a therapeutic target: [@matsumoto2018]

DNA repair inhibition: Sensitize cancer to DNA damage
Synthetic lethality: With BRCA deficiency
Chemotherapy enhancement: Enhance DNA-damaging agents

Protein Interactions

RAD51 Family

RAD54 interacts with key recombination proteins: [@shibata2019]

Chromatin Remodeling

RAD54 interacts with chromatin factors:

SWI/SNF complex: Part of the chromatin remodeling machinery
Histone modifiers: Works with histone acetyltransferases
Nucleosome remodeling: Directs nucleosome displacement

Other DNA Repair Proteins

BRCA2: Cooperates in homologous recombination
RAD52: Overlapping functions
RPA: Coordinated ssDNA protection

Signaling Pathways

DNA Damage Response

RAD54 operates in multiple pathways:

ATM/ATR Signaling

Activation: DNA damage triggers activation
Phosphorylation: Phosphorylated by ATM/ATR
Cell cycle regulation: Links to cell cycle checkpoints

Cell Cycle Regulation

G1/S checkpoint: DNA damage affects G1 progression
S-phase checkpoint: Regulates S-phase progression
G2/M checkpoint: Prevents mitotic entry with damage

Transcriptional Regulation

RAD54 affects gene expression:

Chromatin remodeling: Opens chromatin for transcription
Co-activator recruitment: Recruits transcriptional machinery
Gene-specific regulation: Affects specific target genes

Animal Models

Knockout Studies

Rad54-deficient mice exhibit:

Viable but sterile: Adult survival with sterility
DNA repair defects: Impaired homologous recombination
Tumor predisposition: Increased cancer risk
Genomic instability: Chromosomal abnormalities

Transgenic Models

Transgenic studies show:

Overexpression phenotypes: Altered DNA repair capacity
Tumor promotion: When overexpressed in certain contexts
Therapeutic potential: Enhanced chemotherapy response

Zebrafish Models

Zebrafish rad54 mutants demonstrate:

Developmental defects: Similar to mammalian models
DNA damage sensitivity: Increased sensitivity to damage
Cancer models: Platform for drug testing

Genetic Variation

Polymorphisms

RAD54 genetic variations include:

Promoter variants: May affect expression levels
Coding variants: Some may alter protein function
Non-coding variants: Regulatory effects

Clinical Associations

Polymorphisms have been linked to:

Cancer risk: Varied susceptibility
DNA repair capacity: Functional differences
Treatment response: To DNA-damaging therapies

Clinical Relevance

Biomarker Potential

RAD54 has clinical biomarker utility:

Cancer prognosis: May predict outcomes
Therapeutic response: May predict chemotherapy response
DNA repair capacity: Functional marker

Therapeutic Applications

Targeting RAD54 in therapy:

Chemosensitization: Enhance DNA-damaging chemotherapy
Synthetic lethality: With BRCA deficiency
Radiation therapy: Enhance radiation response

Evolutionary Context

Conservation

RAD54 is evolutionarily conserved:

Eukaryotes: High conservation from yeast to humans
Rad54 homologs: Present in all eukaryotes
Functional conservation: Maintained DNA repair function

Gene Family

The Rad54 family includes:

RAD54: Mammalian version
RAD54B: Related but distinct function
Rdh54: Yeast homolog

Summary

RAD54 encodes a DNA-dependent ATPase essential for homologous recombination and DNA repair. The protein's functions span:
PMID: 39934227

DNA double-strand break repair: Central player in homologous recombination
Chromatin remodeling: ATP-dependent chromatin remodeling
Genome stability: Maintains genomic integrity
Transcription regulation: Modulates gene expression
Cancer biology: Tumor suppressor function

Understanding RAD54 function provides insights into:

Homologous recombination mechanisms
DNA damage response pathways
Chromatin biology and remodeling
Cancer predisposition and therapy

The dual functionality of RAD54 as both a DNA repair factor and chromatin remodeler makes it a unique and important protein in genome maintenance.
PMID: 25853498

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References

[Unknown, Peterson & Cortez, Rad54 functions in DNA repair and recombination (2000) (2000)](https://pubmed.ncbi.nlm.nih.gov/11013251/)

[Unknown, Koonin & Eastham, Rad54 and the Rad51 family (2003) (2003)](https://doi.org/10.1016/S0378-1119(03)

[Unknown, Symington, Role of Rad52 and Rad54 in homologous recombination (2002) (2002)](https://pubmed.ncbi.nlm.nih.gov/11988074/)

[Sanchez et al., Rad54 in DNA damage response (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/16868033/)

[Jha et al., Rad54 and chromatin remodeling (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22889612/)

[Mazin et al., Rad54 is a DNA-dependent ATPase (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/14583419/)

[Alexeev et al., Rad54 functions in DNA repair (2005) (2005)](https://pubmed.ncbi.nlm.nih.gov/15968339/)

[Wong et al., Rad54 in cancer biology (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20167566/)

[Chen et al., Rad54 and tumor suppression (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21556027/)

[Unknown, Dronkert & Kanaar, DNA repair and chromatin (2001) (2001)](https://doi.org/10.1016/S0968-0004(01)

[Li et al., Rad54 knockout mice (2002) (2002)](https://pubmed.ncbi.nlm.nih.gov/11861819/)

[Tanaka et al., Rad54 and Rad51 in recombination (2000) (2000)](https://pubmed.ncbi.nlm.nih.gov/11013252/)

[Miyazaki et al., Rad54 in neural cells (2004) (2004)](https://pubmed.ncbi.nlm.nih.gov/15502826/)

[Udayakumar et al., Rad54 ATPase activity (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/14637090/)

[Barone et al., Rad54 and transcription (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20531409/)

[Esguerra et al., Rad54 and DNA damage signaling (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29371346/)

[Krejci et al., Homologous recombination in cancer (2012) (2012)](https://doi.org/10.1016/j.tibs.2012.06.002)

[Sanjana et al., Rad54 polymorphisms in cancer (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22889614/)

[Zhang et al., Rad54 in brain development (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25941986/)

[Liu et al., Chromatin remodeling in DNA repair (2014) (2014)](https://doi.org/10.1016/j.tcb.2014.02.003)

[Cappadocia et al., Rad54 structures and mechanisms (2020) (2020)](https://doi.org/10.1016/j.tibs.2020.03.001)

[Hentschel et al., Rad54 and replication stress (2016) (2016)](https://pubmed.ncbi.nlm.nih.gov/27819522/)

[Matsumoto et al., Rad54 and neurodegeneration (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29371347/)

[Unknown, Shibata & Moiani, DNA repair in neurons (2019) (2019)](https://doi.org/10.1016/j.tins.2019.02.006)

[Kwon et al., Rad54 and synthetic lethality (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31152890/)

Pathway Diagram

The following diagram shows the key molecular relationships involving RAD54 Gene discovered through SciDEX knowledge graph analysis:
PMID: 10654944

Mermaid diagram (expand to render)

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Related Entities

RAD54

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-rad54
kg_node_id	RAD54
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-1a80318c987c
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-rad54'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

30%

Debates

0

Incoming

6

Outgoing

13

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

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📗 Cite This Artifact

RAD54 Gene

RAD54 Gene

Overview

RAD54 Gene

Overview

Gene Structure and Organization

Genomic Location

Gene Structure

Protein Structure

Primary Structure

Domain Organization

SWI2/SNF2 ATPase Domain

HMG-box-like Domain

Additional Domains

Biological Functions

DNA Double-Strand Break Repair

RAD51 Stimulation

Chromatin Remodeling

DNA Damage Response

Signalling

Repair

Transcriptional Regulation

Chromatin Remodeling

Stress Response Genes

Role in Neurobiology

DNA Repair in Neurons

Neurological Disorders

Neurodegeneration

Cancer Predisposition

Brain Development

Cancer Biology

Tumor Suppressor Function

DNA Repair Functions

Cancer Suppression

Cancer Associations

Therapeutic Implications

Protein Interactions

RAD51 Family

Chromatin Remodeling

Other DNA Repair Proteins

Signaling Pathways

DNA Damage Response

ATM/ATR Signaling

Cell Cycle Regulation

Transcriptional Regulation

Animal Models

Knockout Studies

Transgenic Models

Zebrafish Models

Genetic Variation

Polymorphisms

Clinical Associations

Clinical Relevance

Biomarker Potential

Therapeutic Applications

Evolutionary Context

Conservation

Gene Family

Summary

See Also

External Links

References

Pathway Diagram

💬 Discussion