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

Rebecca Kohnken; Karthik M Kodigepalli; Li Wu

doi:10.1186/s12943-015-0446-6

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

Journal article

Open access

Peer reviewed

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

Rebecca Kohnken, Karthik M Kodigepalli and Li Wu

Molecular cancer, Vol.14(1), pp.176-176

09/29/2015

DOI: 10.1186/s12943-015-0446-6

PMCID: PMC4587406

PMID: 26416562

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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.

Neoplasms - metabolism

Genomic Instability

Cell Proliferation

Neoplasms - genetics

Deoxyribonucleotides - metabolism

Humans

SAM Domain and HD Domain-Containing Protein 1

DNA Replication - genetics

Monomeric GTP-Binding Proteins - genetics

Mutation

Neoplasms - pathology

Deoxyribonucleotides - genetics

Details

Title: Subtitle: Regulation of deoxynucleotide metabolism in cancer: novel mechanisms and therapeutic implications
Creators: Rebecca Kohnken - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH, 43210, USA
Karthik M Kodigepalli - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH, 43210, USA
Li Wu - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA. wu.840@osu.edu
Resource Type: Journal article
Publication Details: Molecular cancer, Vol.14(1), pp.176-176
DOI: 10.1186/s12943-015-0446-6
PMID: 26416562
PMCID: PMC4587406
NLM abbreviation: Mol Cancer
ISSN: 1476-4598
eISSN: 1476-4598
Publisher: England
Grant note: R01 AI104483 / NIAID NIH HHS R21 CA181997 / NCI NIH HHS AI104483 / NIAID NIH HHS T32 OD010429 / NIH HHS CA181997 / NCI NIH HHS
Language: English
Date published: 09/29/2015
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001226602771

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