By Aliza Becker, BA, MPS

Deoxyribonucleic acid (DNA) damage in the body is responsible for both normal aging and the emergence of certain health conditions.¹ The first part of this series examined effects of the diet on the health of telomeres, which cap the ends of individual chromosomes to prevent them from fraying or becoming entangled with one another.² With progressive cell divisions, telomeres become increasingly shorter until the cell can no longer divide successfully and dies.² Shorter telomeres may predispose individuals to a variety of diseases, including cancer, and a greater risk of mortality.³ Research suggests that diet can influence telomere length, with certain foods having different effects depending in part on their pro- or anti-inflammatory potential. The next part of this series examines the impact of diet on DNA replication, with consideration of mutations and repair processes.

DNA replication occurs during the division of existing cells to produce new cells. To ensure that new “daughter” cells have a complete copy of the genome, or the entire set of DNA instructions present within a cell that ultimately tell it how to function, each parent cell replicates its entire genome (S phase) before division (mitosis). Although this process is typically smooth, existing DNA damage prior to the S phase can result in replication of said damaged DNA, which can lead to inherited genetic disorders, cancer, neurological disorders, developmental abnormalities, immune system deficiencies, and premature aging.⁴ Thankfully, DNA repair processes that activate following replication aim to prevent things from getting out of control.

There are a handful of nutrients required for proper DNA replication, with several B vitamins playing crucial roles in nucleotide synthesis. In the body, dietary vitamin B9 (folate) is converted into its active form, tetrahydrofolate (THF), and then into various folate derivatives like 5,10-methylene-THF, which supports the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) through donation of a methyl group from 5,10-methylene-THF to transform uracil (found in dUMP) into thymine (in dTMP).^5,6 dTMP is then phosphorylated to form deoxythymidine triphosphate (dTTP), which serves as a substrate in DNA replication, providing the thymine base necessary for constructing the DNA double helix.^5,7 As such, if folate availability is inadequate, uracil misincorporation into DNA may occur.⁸ This itself is mutagenic, but DNA instability may also occur during the process of uracil removal through base excision repair.⁹ 

Meanwhile, vitamin B12 acts as an essential cofactor for methionine synthase, an enzyme that converts homocysteine to methionine to support the regeneration of THF from 5-methyl-THF (the primary form of folate circulating in the blood); as such, without adequate B12, the availability of THF is decreased, affecting the availability of 5,10-methylene-THF and, consequently, the above-mentioned synthesis of dTMP from dUMP.^5,10 Vitamin B6 also plays a more indirect role in DNA synthesis by acting as a cofactor for the enzyme cystathionine beta-synthase involved in converting homocysteine to cystathionine to help limit homocysteine levels,¹¹ thereby reducing the risk of elevated homocysteine concentrations, which can interfere with folate metabolism by overwhelming the aforementioned pathway of homocysteine to methionine conversion. 

Separately, some minerals also have roles to play. Aside from its stabilizing effect on the structure of DNA through a variety of actions, magnesium is an essential cofactor in almost all enzymatic activities, with roles in several DNA repair processes, including nucleotide excision repair, base excision repair, and mismatch repair.¹² Zinc similarly supports DNA structuring by stabilizing DNA-binding proteins, including transcription factors and some DNA polymerases, and ensures proper enzymatic activity¹³—for example, zinc acts as a cofactor for certain DNA polymerases, supporting their structure and function to help them assemble nucleotides to create the DNA molecule.¹⁴ Zinc is also a cofactor for enzymes involved in DNA repair, including those responsible for nucleotide excision repair and base excision repair.¹⁵ Iron also acts as a cofactor for some DNA polymerases and other related proteins.¹⁶ Moreover, it is a component of ribonucleotide reductase, an enzyme essential for converting ribonucleotides into deoxyribonucleotides, which are required for DNA synthesis.¹⁷ As such, inadequate amounts of these minerals can result in DNA structural or replication problems.¹⁶

Finally, macronutrients are necessary for the synthesis of adenosine triphosphate (ATP), which provides the energy required for various processes in DNA replication. ATP is produced when carbohydrates, proteins, and fats undergo a series of metabolic reactions within a cell’s cytoplasm and mitochondria.¹⁸ Amino acids from proteins are additionally necessary to produce certain proteins required for DNA packaging and repair.¹⁹

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