HomeMedicineInternal MedicineCan folate deficiency lead to irreversible DNA damage?

Can folate deficiency lead to irreversible DNA damage?

In a study published in PNAS, researchers in Denmark examined the effects of folate deficiency on changes to DNA during cell division.

Folate, also known as folic acid or vitamin B9, is an important vitamin found in many fruits and green leafy vegetables. Research has linked folate deficiency to a variety of diseases, including anemia, mental illness, age-related dementia, cancer. Folate deficiency during pregnancy is also associated with birth defects including neural tube defects (brain and spinal cord deformation), which is why folic acid supplements are often recommended for pregnant women.

Folate deficiency has also been linked to Fragile X syndrome, a genetic disease causing mental retardation. When a cell divides, it must replicate all of its DNA and segregate each copy into the two new cells. Fragile X syndrome results from the cell improperly replicating and segregating a specific region of DNA during cell division, leading to major changes (mutations) in this region DNA. These mutations are irreversible and get inherited to all new cells in additional cell divisions.

Though previous research has not examined how folate deficiency leads to associated diseases, the link between folate deficiency and Fragile X syndrome suggests that folate might be important for proper replication and segregation of DNA. Major mutations resulting from improper DNA replication and segregation can also lead to other associated diseases like cancer.

Examining the effects of folate deficiency on DNA replication and segregation

In a study performed at the University of Copenhagen in Denmark and published in the Proceedings of the National Academy of Sciences, researchers investigated a possible link between folate deficiency and improper DNA replication and segregation. Using white blood cells from men with and without Fragile X syndrome, they examined the effects of folate deficiency on replication and segregation of the DNA region affected in Fragile X syndrome.

The researchers found that folate deficiency led to an increase in abnormalities in cell division and segregation of the Fragile X DNA region. These effects were more prominent in cells from men with Fragile X syndrome. When the Fragile X region is already mutated due to improper DNA replication and division, it is more susceptible to further changes.

Maintaining sufficient folate levels may be important for disease prevention

This study was the first to show that folate deficiency leads to improper DNA replication and segregation of DNA into new cells during cell division. Improper replication and division of DNA resulting from deficiency could also be the cause of other folate-deficiency-associated diseases such as age-related dementia and cancer.

One limitation of this study is that researchers only examined the effects of folate deficiency on the Fragile X syndrome DNA region. Further studies are needed to confirm whether deficiency also leads to improper DNA replication and segregation in other regions.

Mutations in DNA caused by folate deficiency are irreversible and passed onto all cells descended from the cell with the original mutation. It thus may be important that people monitor their blood folate levels or take folate supplements to prevent folate deficiency and irreversible DNA damage. If the results of this study extend to all DNA regions, avoiding folate deficiency may greatly reduce one’s risk of diseases such as age-related dementia and cancer.

Written by Melissa H. Wong, MSc

Reference: Bjerregaard VA, Garribba L, McMurray CT, Hickson ID, Liu Y. Folate deficiency drives mitotic missegregation of the human FRAXA locus. 2018. PNAS DOI:10.1073/pnas.1808377115

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