### ERCC2 Gene Overview

**Gene Symbol:** ERCC2 (Excision Repair Cross-Complementation Group 2)

**Function:** The ERCC2 gene encodes a protein that is a critical component of the TFIIH complex, which is involved in transcription-coupled nucleotide excision repair (TC-NER) and plays a role in the general repair of DNA. This protein has ATP-dependent DNA helicase activity, essential for unwinding DNA to facilitate both repair processes and transcription.

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### Additional Associated Genes

1. **XPD (also known as ERCC2)**: As a product of this gene and functionally related to it.
2. **CAK (CDK-activating kinase)**: Interacts with ERCC2 in the transcription pathway.
3. **RAD3**: A homologous gene in yeast, reflecting conserved mechanisms of DNA repair.
4. **ERCC3 (XPD)**: Another member of the nucleotide excision repair pathway involved with ERCC2.
5. **XPB (ERCC3)**: Works in tandem with ERCC2 as a part of the same complex.

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### Aging and Age-Related Disease Associations

- **Cellular Senescence**: While ERCC2 is primarily associated with DNA repair, defects in DNA repair pathways, including those involving ERCC2, contribute to cellular senescence and the aging process. Specifically, impaired DNA repair mechanisms can lead to the accumulation of DNA damage, contributing to aging phenotypes.
- **Cancer Susceptibility**: Individuals with mutations in ERCC2 are more susceptible to skin cancers, including melanoma and nonmelanoma skin cancers. The ability to efficiently repair DNA damage, especially from UV radiation, is critical for preventing these types of cancer. This association hints at potential links between ERCC2 and the aging-related increase in skin cancer risk.
- **Neurodegeneration**: Some studies suggest that deficiencies in nucleotide excision repair involving ERCC2 might be implicated in neurodegenerative diseases, although the exact mechanisms remain to be fully elucidated.

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### Drug Interactions

Currently, specific interactions of drugs or drug classes directly aimed at ERCC2 are not well defined in databases, as ERCC2 itself is not typically targeted therapeutically. However, increasing evidence suggests that:

- **Chemotherapeutic agents**: Some drugs, such as cisplatin, may affect DNA repair pathways, including those in which ERCC2 is involved. Resistance to these drugs has been linked to mutations in ERCC2.
- **Potential anti-aging compounds**: Agents that enhance DNA repair mechanisms may have potential therapeutic links to ERCC2, although formalized relationships require further research.

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### Pathways and Biological Processes

1. **Nucleotide Excision Repair (NER)**: ERCC2 is integral to both global genomic repair (GGR) and transcription-coupled repair (TCR) mechanisms, allowing cells to effectively respond to DNA damage.
2. **Transcription Regulation**: Beyond its DNA repair functions, ERCC2 plays a vital role in the initiation of transcription through its actions on RNA polymerase II and has a part in promoter opening.
3. **Mitotic Spindle Regulation**: As part of the MMXD complex, it is involved in chromosome segregation, indicating its role in maintaining genomic stability during cell division.
4. **Vitamin D Receptor Activity**: ERCC2 has been noted to interact with pathways that regulate the activity of the vitamin D receptor, linking it to metabolic processes.
5. **Cell Cycle Regulation**: ERCC2 may influence various checkpoints in the cell cycle in connection to DNA damage repair processes.

Overall, the ERCC2 gene is multi-functional, influencing key aspects of DNA repair, transcription, and potential implications in aging and cancer susceptibility.