A Critical Balance: dNTPs and the Maintenance of Genome Stability.
A crucial factor in maintaining genome stability is establishing deoxynucleoside triphosphate (dNTP) levels within a range that is optimal for chromosomal replication. Since DNA replication is relevant to a wide range of other chromosomal activities, these may all be directly or indirectly affected when dNTP concentrations deviate from a physiologically normal range. The importance of understanding these consequences is relevant to genetic disorders that disturb dNTP levels, and strategies that inhibit dNTP synthesis in cancer chemotherapy and for treatment of other disorders. We review here how abnormal dNTP levels affect DNA replication and discuss the consequences for genome stability.
CRUK-MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK. chun.pai@oncology.ox.ac.uk.
Chen-Chun
CC
Pai
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. stephen.kearsey@zoo.ox.ac.uk.
Stephen E
SE
Kearsey
DNA polymerase; dNTP; genome instability; proofreading; replication fidelity; ribonucleotide reductase