Bc. Blount et al., FOLATE-DEFICIENCY CAUSES URACIL MISINCORPORATION INTO HUMAN DNA AND CHROMOSOME BREAKAGE - IMPLICATIONS FOR CANCER AND NEURONAL DAMAGE, Proceedings of the National Academy of Sciences of the United Statesof America, 94(7), 1997, pp. 3290-3295
Folate deficiency causes massive incorporation of uracil into human DN
A (4 million per cell) and chromosome breaks, The likely mechanism is
the deficient methylation of dUMP to dTMP and subsequent incorporation
of uracil into DIVA by DNA polymerase. During repair of uracil in DNA
, transient nicks are formed; two opposing nicks could lead to chromos
ome breaks, Both high DNA uracil levels and elevated micronucleus freq
uency (a measure of chromosome breaks) are reversed by folate administ
ration. A significant proportion of the U.S. population has low folate
levels, in the range associated with elevated uracil misincorporation
and chromosome breaks, Such breaks could contribute to the increased
risk of cancer and cognitive defects associated with folate deficiency
in humans.