### POLD2 Gene Overview

**Gene Symbol:** POLD2  
**Location:** 13q33.1 (human chromosome 13)  
**Protein Structure:** Encodes a 50-kDa catalytic subunit of DNA polymerase delta.

### Key Features:

1. **Function & Activity:**
   - POLD2 encodes a subunit of DNA polymerase delta, essential for high-fidelity DNA replication and repair.
   - It possesses both polymerase activity and 3' to 5' exonuclease activity, allowing for proofreading during DNA synthesis.
   - It is critical for the stimulation of DNA polymerase by the processivity cofactor proliferating cell nuclear antigen (PCNA).
   - Participates in the bypass of DNA lesions and is involved in translesion synthesis (TLS).

2. **Complex Formation:**
   - Component of both DNA polymerase delta and DNA polymerase zeta complexes, influencing their assembly and functional diversity.
   - Exists in different complexes, Pol-delta3 (lacking POLD4) and Pol-delta4 (containing POLD4), with differing catalytic activities and efficiencies.

3. **Alternative Splicing:**
   - Multiple isoforms resulting from alternative splicing have been reported, which may influence its functional roles in cells.

4. **Clinical Relevance:**
   - Elevated expression may serve as a biomarker for ovarian carcinomas.
   - Implicated in responses to DNA replication stress, which is particularly relevant in the context of cancer biology.

### Additional Associations

1. **Associated Genes:**
   - **POLD1:** Another subunit of DNA polymerase delta with significant functional interplay, particularly in DNA replication.
   - **POLD3 and POLD4:** Other subunits of DNA polymerase delta influencing the complex's activity and processivity.
   - **REV3L and REV7:** Subunits of DNA polymerase zeta involved in translesion synthesis.

2. **Aging and Age-Related Diseases:**
   - POLD2 and its activity have been associated with DNA repair mechanisms which decline with age, leading to genomic instability.
   - Deficient DNA repair is linked to age-related diseases, including cancer and neurodegenerative conditions. Changes in the expression of DNA polymerase enzymes, including those involving POLD2, could contribute to the mechanisms underlying these age-related diseases.

3. **Drug Interactions:**
   - While specific drugs directly targeting POLD2 are limited, the poly(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, indirectly interact with DNA repair pathways that involve POLD2.
   - Drugs used in cancer treatment, particularly those affecting DNA replication and repair processes, may also have an indirect impact on the function of DNA polymerases including POLD2.

4. **Involved Pathways and Biological Processes:**
   - **DNA Replication:** Critical role in the synthesis of both the leading and lagging strands.
   - **DNA Repair:** POLD2 is involved in nucleotide excision repair (NER) and mismatch repair mechanisms.
   - **Translesion DNA Synthesis:** Facilitating DNA polymerase's ability to synthesize over DNA lesions.
   - **Cell Cycle Regulation:** Plays a role in cell cycle progression, especially during the S phase when DNA is replicated.
   - **Break-Induced Replication (BIR):** Functions under conditions of replication stress to repair broken forks.

### Summary

The POLD2 gene is integral to the function of DNA polymerase delta, playing a key role in DNA replication and repair. Its activity is vital for cellular integrity and has implications in cancer biology and aging. Understanding POLD2's interactions and influences can aid in the development of therapeutic strategies, particularly in oncology.