MDC1 (Mediator of DNA Damage Checkpoint 1) is a DNA damage response protein that plays a crucial role in the recognition and repair of DNA double-strand breaks. MDC1 acts as a scaffold protein, recruiting repair factors to sites of DNA damage. It has been implicated in neurodegenerative diseases where DNA repair mechanisms are compromised.
| Symbol | MDC1 |
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| Full Name | Mediator of DNA Damage Checkpoint 1 |
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| Chromosomal Location | 6p21.33 |
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| NCBI Gene ID | [9657](https://www.ncbi.nlm.nih.gov/gene/9657) |
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| OMIM | [607618](https://www.omim.org/entry/607618) |
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| Ensembl ID | ENSG00000137336 |
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| UniProt ID | [Q9Y2E5](https://www.uniprot.org/uniprot/Q9Y2E5) |
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| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Ataxia-Telangiectasia](/diseases/ataxia-telangiectasia) |
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MDC1 is a key mediator protein in the DNA damage response (DDR) pathway. It functions as a molecular scaffold to recruit and retain DNA repair proteins at sites of DNA double-strand breaks.
- FHA Domain: Forkhead-associated domain for protein interactions
- BRCT Domains: Breast cancer C-terminal domains for phospho-Ser/Thr binding
- SDT Repeats: Ser-Asp-Thr repeats for ATM phosphorylation sites
- NBS1-Binding Region: Mediates interaction with NBS1/MRE11/RAD50 complex
- DNA Damage Recognition: Recognizes gamma-H2AX at DNA break sites
- Scaffold Function: Recruits NBS1, BRCA1, and 53BP1 to damage sites
- Cell Cycle Checkpoint: Facilitates ATM/ATR-mediated checkpoint activation
- Chromatin Remodeling: Promotes chromatin changes for repair
- Neuronal DNA Repair: Critical for maintaining neuronal genome integrity
- DNA Repair Impairment: AD neurons show reduced DNA repair capacity
- Genomic Instability: Accumulation of DNA damage in AD brain
- Therapeutic Target: Enhancing MDC1 function may protect neurons
- Reference: Thadathil et al., Aging Cell (2022)
- Cerebral Cortex: Moderate to high expression
- Hippocampus: High expression in neurons
- Cerebellum: Present in Purkinje cells
- Substantia Nigra: Detected in dopaminergic neurons
- Nuclear: Predominantly nuclear
- DNA Damage Sites: Rapidly localizes to sites of DNA damage
- Chromatin-Bound: Associates with chromatin
| Variant |
Function |
Disease Association |
| IVS5-1G>A |
Splicing |
Possible cancer risk |
| E700K |
Missense |
None confirmed |
| 2295delC |
Frameshift |
Possible cancer risk |
- MDC1 expression as indicator of DNA damage burden
- Potential therapeutic monitoring marker