Inhibition of Dr‐dut gene causes DNA damage in planarian

Inhibition of Dr‐dut gene causes DNA damage in planarian AbbreviationsATMAtaxia telangiectasia‐mutatedATRATM‐ and Rad3‐relateddUTPaseDeoxyuridine triphosphatase (encoded by the DUT gene)PCNAProliferating cell nuclear antigenRNAiRNA interference.INTRODUCTIONThe DUT gene encodes the enzyme Deoxyuridine triphosphatase (dUTPase), which hydrolyzes dUTP to dUMP and pyrophosphate. In the pyrimidine biosynthetic pathway, dUTP is produced by deoxygenation of UTP, deamination of dCTP, or phosphorylation of dUDP (Bertani, Hiiggmark, & Reichard, ; Frederico, Kunkel, & Shaw, ; Johansson, Bjornberg, Nyman, & Larsen, ; O'donovan, Edlin, Fuchs, Neuhard, & Thomassen, ). DNA, however, requires dTTP, which is produced via four contentious reactions: (i) the formation of dUMP by removal of diphosphate from dUTP (catalyzed by dUTPase); (ii) the uridine‐thymidine transition by Thymidylate synthase; and (iii‐iv) the two‐step kination of dTMP (Pyrimidine metabolism KEGG pathway; www.genome.jp/kegg/pathway/map/map00240.html). The production of dUTP can occur via three routes, whereas that of dTTP has only one, leaving mitogenic cells somewhat vulnerable to dTTP deficiencies. dUTPase helps regulate the dUTP‐to‐dTTP ratio, which is a critical enzymatic function for cell homeostasis (Vértessy & Tóth, ) because the DNA polymerase‐dependent incorporation of dUTP instead of dTTP will eventually induce apoptosis and possibly cause lethality (Ahmad, Kirk, & Eisenstark, ).High abundance of uracil in DNA overloads the uracil‐directed base‐excision repair mechanism (Castillo‐Acosta et al., ; Koehler & Ladner, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Reproduction & Development Wiley

Inhibition of Dr‐dut gene causes DNA damage in planarian

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Publisher
Wiley
Copyright
© 2018 Wiley Periodicals, Inc.
ISSN
1040-452X
eISSN
1098-2795
D.O.I.
10.1002/mrd.22952
Publisher site
See Article on Publisher Site

Abstract

AbbreviationsATMAtaxia telangiectasia‐mutatedATRATM‐ and Rad3‐relateddUTPaseDeoxyuridine triphosphatase (encoded by the DUT gene)PCNAProliferating cell nuclear antigenRNAiRNA interference.INTRODUCTIONThe DUT gene encodes the enzyme Deoxyuridine triphosphatase (dUTPase), which hydrolyzes dUTP to dUMP and pyrophosphate. In the pyrimidine biosynthetic pathway, dUTP is produced by deoxygenation of UTP, deamination of dCTP, or phosphorylation of dUDP (Bertani, Hiiggmark, & Reichard, ; Frederico, Kunkel, & Shaw, ; Johansson, Bjornberg, Nyman, & Larsen, ; O'donovan, Edlin, Fuchs, Neuhard, & Thomassen, ). DNA, however, requires dTTP, which is produced via four contentious reactions: (i) the formation of dUMP by removal of diphosphate from dUTP (catalyzed by dUTPase); (ii) the uridine‐thymidine transition by Thymidylate synthase; and (iii‐iv) the two‐step kination of dTMP (Pyrimidine metabolism KEGG pathway; www.genome.jp/kegg/pathway/map/map00240.html). The production of dUTP can occur via three routes, whereas that of dTTP has only one, leaving mitogenic cells somewhat vulnerable to dTTP deficiencies. dUTPase helps regulate the dUTP‐to‐dTTP ratio, which is a critical enzymatic function for cell homeostasis (Vértessy & Tóth, ) because the DNA polymerase‐dependent incorporation of dUTP instead of dTTP will eventually induce apoptosis and possibly cause lethality (Ahmad, Kirk, & Eisenstark, ).High abundance of uracil in DNA overloads the uracil‐directed base‐excision repair mechanism (Castillo‐Acosta et al., ; Koehler & Ladner,

Journal

Molecular Reproduction & DevelopmentWiley

Published: Jan 1, 2018

Keywords: ; ; ;

References

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