In a study recently published in the scientific journal PNAS, researchers from the DNRF’s Center for Chromosome Stability (CCS) at the University of Copenhagen have found that deficiency in vitamin B folate can lead to hitherto unknown problems in connection to DNA replication with cell division. Once you suffer from folate deficiency, it is not possible to recover from the damage it can cause.
A number of biological processes ensure that our bodies are maintained throughout life, and one of the most important processes is cell division, whereby DNA and the cells in the rest of our bodies are replicated. At times, errors can occur in the division process, which can lead to chromosome faults and mutations in the new cells. In a new study, Associate Professor Ying Liu, from the DNRF Center of Excellence CCS, led a research group that found how folate deficiency can lead to hitherto unknown problems with cell division. Folate is a type of vitamin B that can be found in several foods such as green vegetables, seafood, and wheat products.
“In the study, we demonstrate that folate deficiency leads to both higher levels of and more harmful chromosome abnormalities than previously known. This causes the daughter cells to inherit the incorrect amount of DNA following cell division or, in some cases, to even lose an entire chromosome. This could explain why folate deficiency is associated with diseases like infertility, mental health disorders, and cancer,” explained Associate Professor Ying Liu, head of group at CCS and senior author behind the study.
The level of folate can be measured with the help of a blood sample, and researchers have long known how a lack of folate is connected to mental illness, age-related dementia, and deformation of the brain and spinal cord of fetuses, also known as neural tube defects. However, it has not yet been proven whether folate deficiency is the direct cause of these illnesses or if the diseases are caused by a secondary effect of the lack of folate. The researchers from CCS examined this question by studying so-called lymphocytes, a type of white blood cell that, in the study, came from men, but the results, according to Associate Professor Liu, can be applied to women as well.
“Once the damage is done, it is irreversible”
Liu and the rest of the research team then analyzed a part of the genome called FRAXA, which contains an extensive CGG sequence – a genetic code. Here, the researchers discovered that folate deficiency created abnormalities during the mitosis phase, which is the actual cell division – especially in cells with an abnormal long CGG sequence. The abnormalities would show up, for instance, as a faulty segregation of chromosomes.
Furthermore, the researchers also saw that the entire X chromosome became unstable in cases of long-term folate deficiency, which can lead to the chromosomal disease Klinefelter’s syndrome, which can cause infertility.
“The problem with folate deficiency is that it affects chromosome maintenance, and once a cell has lost a chromosome or part of it, it can never be fixed. That is, once cell division has gone wrong, you cannot fix it subsequently by consuming a lot of folic acid. Once the damage is done, it is irreversible.” Associate Professor Liu said and added:
“Therefore, we need a guide telling us what the level of folate in the blood in the population in general should be. Once we have that knowledge, we can determine whether a person needs folic acid supplements to make sure the level in the blood is high enough for the cells to reproduce the DNA successfully.”