Human populations are routinely exposed to synthetic compounds through food, water, air, and consumer products. Key findings from large-scale studies include:
Notable compounds: Poly- and perfluoroalkyl substances (PFAS), phthalates, and bisphenols dominate exposure profiles due to their persistence and bioaccumulation .
Health correlations: PFAS exposure is linked to immune suppression, thyroid dysfunction, and developmental delays .
The Tox21 1000 Genomes Project analyzed cytotoxicity responses to 156 compounds across 884 lymphoblastoid cell lines, revealing:
Population variability: Cytotoxicity predictions showed modest correlations (Pearson's r < 0.28) at the individual level but higher accuracy (r < 0.66) for population-level responses .
Predictability clusters: Compounds like Lipinski rule-compliant molecules exhibited higher predictability due to multimodal cytotoxicity distributions .
Emerging tools: High-coverage genome sequencing (35x) has identified 929 million SNPs across 54 populations, enhancing precision in exposure studies .
While not directly related to synthetic compounds, baseline elemental data contextualize bioaccumulation risks:
Element | % Mass | Key Biological Roles |
---|---|---|
Oxygen | 65.0 | Cellular respiration, water |
Carbon | 18.5 | Organic molecules, lipids |
Hydrogen | 9.5 | Metabolic water, pH balance |
Nitrogen | 2.6 | Proteins, nucleic acids |
Trace elements like lead and mercury—though constituting <0.1% of mass—pose disproportionate toxicity risks at low concentrations .
The recombinant form of DNA Polymerase Lambda is typically produced in Escherichia coli (E. coli). It is a single, non-glycosylated polypeptide chain containing 320 amino acids, with a molecular mass of approximately 36.0 kDa . The recombinant enzyme is often fused to a 20 amino acid His-tag at the N-terminus to facilitate purification through chromatographic techniques .
DNA Polymerase Lambda plays a crucial role in several DNA repair pathways, including:
Base Excision Repair (BER): This pathway is responsible for repairing lesions that give rise to abasic (AP) sites in DNA . Pol λ has both template-dependent and template-independent (terminal transferase) DNA polymerase activities, which are essential for filling in the gaps left after the removal of damaged bases .
Non-Homologous End Joining (NHEJ): Pol λ contributes to the repair of DNA double-strand breaks by NHEJ, a process that directly ligates the broken ends without the need for a homologous template .
Homologous Recombination (HR): In addition to NHEJ, Pol λ is also involved in HR, a more accurate repair mechanism that uses a homologous sequence as a template for repair .
5’-Deoxyribose-5-Phosphate Lyase (dRP Lyase) Activity: Pol λ possesses dRP lyase activity, which is crucial for the removal of the 5’-deoxyribose phosphate group during BER .
Mutations or deficiencies in the POLL gene can lead to various genetic disorders. For instance, Split-Hand/Foot Malformation 1 and Adams-Oliver Syndrome have been associated with mutations in this gene . Additionally, the enzyme’s role in DNA repair pathways makes it a potential target for cancer therapy, as defects in these pathways are often linked to cancer development .
Recombinant DNA Polymerase Lambda is widely used in research to study DNA repair mechanisms and to develop potential therapeutic interventions. Its ability to perform both template-dependent and template-independent DNA synthesis makes it a valuable tool in molecular biology and genetic engineering .
In summary, Polymerase (DNA directed), Lambda (Human Recombinant) is a versatile and essential enzyme involved in maintaining genomic stability through its roles in various DNA repair pathways. Its recombinant form provides a valuable resource for scientific research and potential therapeutic applications.