Format

Send to

Choose Destination
Mol Cancer. 2015 Sep 29;14:176. doi: 10.1186/s12943-015-0446-6.

Regulation of deoxynucleotide metabolism in cancer: novel mechanisms and therapeutic implications.

Author information

1
Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH, 43210, USA.
2
Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH, 43210, USA. wu.840@osu.edu.
3
Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, 43210, USA. wu.840@osu.edu.
4
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA. wu.840@osu.edu.

Abstract

Regulation of intracellular deoxynucleoside triphosphate (dNTP) pool is critical to genomic stability and cancer development. Imbalanced dNTP pools can lead to enhanced mutagenesis and cell proliferation resulting in cancer development. Therapeutic agents that target dNTP synthesis and metabolism are commonly used in treatment of several types of cancer. Despite several studies, the molecular mechanisms that regulate the intracellular dNTP levels and maintain their homeostasis are not completely understood. The discovery of SAMHD1 as the first mammalian dNTP triphosphohydrolase provided new insight into the mechanisms of dNTP regulation. SAMHD1 maintains the homeostatic dNTP levels that regulate DNA replication and damage repair. Recent progress indicates that gene mutations and epigenetic mechanisms lead to downregulation of SAMHD1 activity or expression in multiple cancers. Impaired SAMHD1 function can cause increased dNTP pool resulting in genomic instability and cell-cycle progression, thereby facilitating cancer cell proliferation. This review summarizes the latest advances in understanding the importance of dNTP metabolism in cancer development and the novel function of SAMHD1 in regulating this process.

PMID:
26416562
PMCID:
PMC4587406
DOI:
10.1186/s12943-015-0446-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center