Introduction
  Life  as  we  know  it  depends  entirely  on  the  capacity  of  cells  to  utilize  energy  and 
  molecules in the environment for cellular function and reproduction. 
  Multicellular animal organisms, including humans, acquire energy and essential nutrients 
  from foods. 
  Some of these essential nutrients are required for DNA synthesis, maintenance of normal 
  chromosome structure,  repair  of  DNA  damage  caused  by  nutrient  deficiency  and/or 
  environmental  genotoxins,  and  for  the  control  of  gene  expression  by  epigenetic 
  mechanisms. 
  This review provides a brief outline of the role of nutrition in DNA replication, DNA 
  damage prevention and DNA repair.
   Role of Nutrition in DNA replication, DNA damage prevention and DNA repair
   At the most basic level nutrition plays an important role by providing essential precursor 
   molecules for the de novo synthesis of purine and pyrimidine nucleotides that determine 
   the genetic code in DNA [1]. 
   Examples of precursor molecules provided by nutrition that are required for nucleotide 
   synthesis are methyl donors such as folate, vitamin B12 and methionine. 
   Folate plays a critical role in the de novo synthesis of purines as 10-formyl 
   tetrahydrofolate, and in the synthesis of pyrimidines as 5,10-methylenetetrahydrofolate by 
   donating formyl and methyl moieties respectively (Figure 1, next slide). 
                                           De Novo Nucleotide Synthesis
                              Purines                  Ribose-5-P               Pyrimidines
                                                      THF
                                                     l 
                                                    y
                                                   m
                                  IMP            or
                                                f
                                              0-                                UMP                dUMP
                                             1
                      AMP                    GMP                                                       5,10-meTHF
                                                                                 UTP
                      ATP                    GTP                                 CTP               dTTP
  Furthermore, 
  5-methyltetrahydrofolate is required for synthesis of methionine. 
  Methionine is essential for the synthesis of S-adenosyl methionine (SAM) which is the 
  common methyl donor
   
  SAM is required for the conversion of cytosine to 5-methylcytosine, the fifth 
  nucleotide in DNA. 
  5-methylcytosine plays a critical role in:
   
  (i) structural chromosome stability, particularly in the pericentromeric region; and 
  (ii)maintenance of DNA methylation patterns that control normal cellular gene 
   expression and phenotype in response to environmental cues. 
  Vitamin B12 is vital in DNA metabolism because it determines the availability of folate 
  for nucleotide and methionine synthesis due to its role as an essential cofactor for the 
  enzyme  methionine  synthase,  which  enables  the  transfer  of  a  methyl  group  from  5-
  methyltetrahdrofolate to homocysteine to generate methionine and tetrahydrofolate (THF). 
  Tetrahydrofolate  (THF)  is  the  form  of  folate  that  can  be  stored  in  cells  after 
  polyglutamation. 
  THF is required as a precursor to generate (i) 10-formyl tetrahydrofolate essential for 
  purine nucleotide (ATP, GTP) synthesis; and (ii) 5,10-methylenetetrahydrofolate, required 
  for pyrimidine nucleotide synthesis (TTP, CTP). 
  When vitamin B12 and/or folate are deficient the cell cannot generate enough nucleotides 
  to  properly replicate DNA, leading to DNA replication stress, DNA strand breaks and 
  chromosome aberrations.