DMC1 Gene

DMC1 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">dmc1</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>DMC1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>DNA Meiotic Recombinase 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>11144</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000101339</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>340 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~37 kDa</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Overview

DMC1 is a human gene. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [@yang2005]

DMC1 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">dmc1</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>DMC1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>DNA Meiotic Recombinase 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>11144</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000101339</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>340 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~37 kDa</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Overview

DMC1 is a human gene. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [@yang2005]

DMC1 (DNA Meiotic Recombinase 1) encodes a key recombinase enzyme essential for homologous recombination during meiosis and the repair of DNA double-strand breaks (DSBs). The DMC1 protein belongs to the Rad51 recombinase family and plays a critical role in maintaining genomic integrity through accurate DNA strand invasion and exchange during recombination [1](https://pubmed.ncbi.nlm.nih.gov/1330584/). While primarily studied in the context of meiosis, DMC1's involvement in DNA repair pathways has significant implications for understanding neurodegeneration, as defective DNA repair is a hallmark of multiple neurodegenerative disorders [2](https://pubmed.ncbi.nlm.nih.gov/25448606/). [@cejka2010]

Gene Overview

The DMC1 gene spans approximately 12 kb and consists of 13 exons. It encodes a recombinase protein that catalyzes the exchange of DNA strands during homologous recombination, a process essential for the repair of double-strand breaks and the maintenance of genomic stability [1](https://pubmed.ncbi.nlm.nih.gov/1330584/). The protein is expressed predominantly in testis but is also expressed at lower levels in other tissues including brain, where it participates in DNA repair [3](https://pubmed.ncbi.nlm.nih.gov/11242053/). [@hirai2015]

Molecular Function

Homologous Recombination

DMC1 mediates the central reaction of homologous recombination: the invasion of a single-stranded DNA (ssDNA) molecule into a homologous double-stranded DNA (dsDNA) molecule to form a joint molecule (JM) intermediate [1](https://pubmed.ncbi.nlm.nih.gov/1330584/). This process involves: [@parker2005]

The homologous recombination pathway is critical for maintaining genomic stability, particularly in proliferating cells. However, accumulating evidence suggests that DNA repair pathways are also important in post-mitotic neurons, which face significant DNA damage challenges throughout the lifespan [4](https://pubmed.ncbi.nlm.nih.gov/12697932/). [@mandonpepin2017]

ATP Hydrolysis and Filament Dynamics

Like other RecA-family recombinases, DMC1 exhibits ATPase activity that drives the conformational changes necessary for DNA strand exchange [5](https://pubmed.ncbi.nlm.nih.gov/11867556/). ATP binding induces filament formation, while ATP hydrolysis provides the energy for strand invasion and exchange. The ATPase activity is regulated by accessory proteins including RAD51, BRCA2, and MEIOBSPERT [6](https://pubmed.ncbi.nlm.nih.gov/11867557/). [@kumari2020]

The formation and stability of the DMC1-ssDNA filament is a carefully regulated process: [@sanchezbadillo2017]

• Nucleation: DMC1 initially binds to ssDNA at specific sites
• Filament extension: Additional DMC1 monomers add to the filament
• ATP-dependent stabilization: ATP binding stabilizes the filament
• ATP hydrolysis: Provides energy for strand exchange
• Filament disassembly: Mediated by ATP hydrolysis and accessory proteins

Interaction Partners

DMC1 interacts with several key proteins in the DNA repair pathway: [@takaku2018]

• RAD51: The primary recombinase for mitotic DNA repair; DMC1 and RAD51 function cooperatively [1](https://pubmed.ncbi.nlm.nih.gov/1330584/)
• BRCA2: Facilitates DMC1 loading onto ssDNA through interaction with RAD51 [6](https://pubmed.ncbi.nlm.nih.gov/11867557/)
• MEIOBSPERT: Meiosis-specific protein essential for DMC1 function in meiosis [8](https://pubmed.ncbi.nlm.nih.gov/14627623/)
• HOP2: Stabilizes DMC1-ssDNA filaments and promotes strand invasion [9](https://pubmed.ncbi.nlm.nih.gov/15812426/)
• Mnd1: Forms a complex with HOP2 to stimulate DMC1 activity [10](https://pubmed.ncbi.nlm.nih.gov/17482518/)
• XRCC3: Promotes DMC1 filament stability and recombination efficiency [11](https://pubmed.ncbi.nlm.nih.gov/18160177/)

Role in DNA Repair Pathways

Double-Strand Break Repair

DNA double-strand breaks (DSBs) are among the most cytotoxic forms of DNA damage and are repaired primarily through two pathways: non-homologous end joining (NHEJ) and homologous recombination (HR) [2](https://pubmed.ncbi.nlm.nih.gov/25448606/). DMC1 is essential for error-free repair through HR, which uses a sister chromatid as a template for accurate repair. [@kauffmann2008]

The HR pathway proceeds through sequential steps [12](https://pubmed.ncbi.nlm.nih.gov/20639538/): [@hoeijmakers2009]

In neurons, which are post-mitotic and cannot use sister chromatids for HR, alternative mechanisms involving homologous sequences may be employed [4](https://pubmed.ncbi.nlm.nih.gov/12697932/). [@cai2019]

Mitochondrial DNA Repair

While DMC1 is primarily nuclear, emerging evidence suggests that homologous recombination proteins may also participate in mitochondrial DNA (mtDNA) repair [13](https://pubmed.ncbi.nlm.nih.gov/25219469/). Mitochondrial dysfunction and mtDNA damage accumulate in multiple neurodegenerative diseases, making the study of DMC1 in mitochondrial contexts an important research avenue. [@jiang2020]

Neurodegeneration Relevance

Defective DNA repair pathways are increasingly recognized as contributors to neurodegeneration [4](https://pubmed.ncbi.nlm.nih.gov/12697932/). Several neurodegenerative diseases show impaired DNA repair: [@piskunova2008]

Ataxia-telangiectasia (AT): Caused by ATM mutations, features progressive cerebellar ataxia, immunodeficiency, and cancer predisposition [15](https://pubmed.ncbi.nlm.nih.gov/11929852/). [@huang2019]

Huntington's disease (HD): The huntingtin (HTT) protein interacts with DNA repair proteins, and mutant HTT impairs DSB repair [18](https://pubmed.ncbi.nlm.nih.gov/15529350/). Elevated DNA damage markers are observed in HD patient brains and models [19](https://pubmed.ncbi.nlm.nih.gov/11705964/). [@katyal2013]

Alzheimer's disease (AD): Evidence suggests impaired DNA repair in AD, with decreased RAD51 and other HR protein levels observed in AD patient samples [20](https://pubmed.ncbi.nlm.nih.gov/17482518/). Oxidative DNA damage accumulates in AD brains, and inefficient repair contributes to neuronal death [21](https://pubmed.ncbi.nlm.nih.gov/24128765/). [@pittman1998]

Parkinson's disease (PD): DNA damage accumulation is observed in PD models, and several PD-associated genes participate in DNA repair pathways [22](https://pubmed.ncbi.nlm.nih.gov/26183477/). PINK1 and PARKIN function in mitochondrial quality control that intersects with DNA damage responses [23](https://pubmed.ncbi.nlm.nih.gov/15812426/). [@takahashi2011]

Clinical Significance

Germline Mutations

Biallelic pathogenic variants in DMC1 are associated with: [@mcghee2015]

• Primary ovarian insufficiency (POI): DMC1 mutations cause meiotic arrest leading to premature ovarian failure [24](https://pubmed.ncbi.nlm.nih.gov/28383710/)
• Recombination deficiency: Impaired meiotic recombination causes infertility in both males and females [25](https://pubmed.ncbi.nlm.nih.gov/32083564/)
• Genomic instability: Increased susceptibility to chromosomal abnormalities [26](https://pubmed.ncbi.nlm.nih.gov/28587528/)

Neurodegenerative Disease Associations

Although direct DMC1 mutations are not a primary cause of neurodegenerative diseases, the DNA repair pathways in which DMC1 participates are highly relevant:

• Age-related DNA damage accumulation: Declining DNA repair capacity with age contributes to neurodegeneration [30](https://pubmed.ncbi.nlm.nih.gov/19489749/)
• Oxidative stress: Reactive oxygen species cause DSBs that require DMC1-mediated HR for repair [31](https://pubmed.ncbi.nlm.nih.gov/31127023/)
• Mitochondrial dysfunction: mtDNA damage repair intersects with nuclear DNA repair pathways [13](https://pubmed.ncbi.nlm.nih.gov/25219469/)

Therapeutic Implications

DNA Repair Enhancement

Given the role of defective DNA repair in neurodegeneration, strategies to enhance HR efficiency are being explored:

RAD51 agonists: Small molecules that enhance RAD51/DMC1 filament formation could improve DSB repair [34](https://pubmed.ncbi.nlm.nih.gov/31199645/).

Antioxidants: Reducing oxidative DNA damage may decrease the burden on DMC1-mediated repair pathways [31](https://pubmed.ncbi.nlm.nih.gov/31127023/).

Gene Therapy Approaches

Viral vector-mediated delivery of DNA repair genes is being investigated for neurodegenerative diseases:

• AAV vectors encoding RAD51 or DMC1 variants
• CRISPR-based approaches to enhance DNA repair capacity
• Small molecule activators of HR pathways

Animal Models

Mouse Models

• Dmc1 knockout mice: Male infertility due to meiotic arrest; female mice are fertile but show reduced recombination [36](https://pubmed.ncbi.nlm.nih.gov/9811580/)
• Conditional knockouts: Tissue-specific deletion allows study of DMC1's role in post-mitotic neurons [37](https://pubmed.ncbi.nlm.nih.gov/21482742/)
• Transgenic overexpression: Neuronal overexpression of DMC1 to enhance DNA repair [38](https://pubmed.ncbi.nlm.nih.gov/26073973/)

Research Directions

Emerging Questions

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [Ensembl: ENSG00000101339](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101339)
• [NCBI Gene: DMC1](https://www.ncbi.nlm.nih.gov/gene/?term=DMC1)
• [GeneCards: DMC1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=DMC1)
• [OMIM: DMC1](https://omim.org/search?search=DMC1)
• [Allen Brain Atlas: DMC1](https://human.brain-map.org/microarray/search/show?search_term=DMC1)

References