Nucleotide Pool

Intracellular free mononucleotides play essential roles as precursors in the synthesis of DNA and RNA, and as molecules for energy storage, cofactors of metabolic pathways and regulators of signal transduction. Given that more than ten-billion molecules of mononucleotides are required for an entire replication of human genome, the quality control of nucleotide pool -- "a source of mononucleotides" -- is undoubtedly important for maintaining the integrity of genomic DNA. Free nucleotides can, however, undergo various chemical modifications by endogenous and exogenous reactive molecules, some of which are inevitably produced in living cells. Chemical modifications may alter the properties of nucleotides, including their interaction with other molecules. Some modified deoxynucleotides are known to be incorporated into and to accumulate in newly synthesized DNA during DNA replication. Modified nucleotides, accumulated in either the nucleotide pool or DNA, may inhibit DNA or RNA polymerases during replication or transcription, reduce polymerase fidelity or alter the DNA structure, thus resulting in mutagenesis and carcinogenesis, cell death and degenerative disorders or senescence and aging. In addition to DNA metabolism, the other biological functions of canonical nucleotides may also be adversely affected by modified nucleotides. The aim of our study is to identify and investigate the molecules essential for the maintenance of the nucleotide pool homeostasis. This movie has ...
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