DNA lesion bypass polymerases and 4'-thio-β-D-arabinofuranosylcytosine (T-arac)

Yih Wen Chen, Kai Ming Chou

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The 4'-thio-(3-D-arabinofuranosylcytosine (T-araC) is a newly developed nucleoside analog that has shown promising activity against a broad spectrum of human solid tumors in both cellular and xenograft mice models. T-araC shares similar structure with another anticancer deoxycytidine analog, (3-D-arabinofuranosylcytosine (araC, cyta-rabine), which has been used in clinics for the treatment of acute myelogenous leukemia but has a very limited efficacy against solid tumors T-araC exerts its anticancer activity mainly by inhibiting replicative DNA polymerases from further extension after its incorporation into DNA. DNA lesion bypass polymerases can manage the DNA lesions introduced by therapeutic agents, such as cisplatin and araC, therefore reduce the activity of these compounds. In this study, the potential relationships between the lesion bypass Y-family DNA polymerases n, i and k (pol n, pol i, and pol k) and T-araC were examined. Biochemical studies indicated that the triphosphate metabolite of T-araC is a less preferred substrate for the Y-family polymerases. In addition, cell viability study indicated that pol n. deficient human fibroblast cells were more sensitive to T-araC when compared with the normal human fibroblast cells. Together, these results suggest that bypass polymerases reduced cell sensitivity to T-araC through helping cells to overcome the DNA damages introduced by T-araC.

Original languageEnglish (US)
Pages (from-to)340-346
Number of pages7
JournalInternational Journal of Biochemistry and Molecular Biology
Volume2
Issue number4
StatePublished - 2011
Externally publishedYes

Fingerprint

Cytarabine
DNA
Cells
DNA-Directed DNA Polymerase
Fibroblasts
Tumors
4'-thio-arabinofuranosylcytosine
Deoxycytidine
Metabolites
Nucleosides
Heterografts
Acute Myeloid Leukemia
Cisplatin
DNA Damage
Neoplasms
Cell Survival
Substrates

Keywords

  • araC
  • Bypass polymerases
  • Nucleoside analogs

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

DNA lesion bypass polymerases and 4'-thio-β-D-arabinofuranosylcytosine (T-arac). / Chen, Yih Wen; Chou, Kai Ming.

In: International Journal of Biochemistry and Molecular Biology, Vol. 2, No. 4, 2011, p. 340-346.

Research output: Contribution to journalArticle

@article{7f61bbd59d4d498b8528ae4445bf9f81,
title = "DNA lesion bypass polymerases and 4'-thio-β-D-arabinofuranosylcytosine (T-arac)",
abstract = "The 4'-thio-(3-D-arabinofuranosylcytosine (T-araC) is a newly developed nucleoside analog that has shown promising activity against a broad spectrum of human solid tumors in both cellular and xenograft mice models. T-araC shares similar structure with another anticancer deoxycytidine analog, (3-D-arabinofuranosylcytosine (araC, cyta-rabine), which has been used in clinics for the treatment of acute myelogenous leukemia but has a very limited efficacy against solid tumors T-araC exerts its anticancer activity mainly by inhibiting replicative DNA polymerases from further extension after its incorporation into DNA. DNA lesion bypass polymerases can manage the DNA lesions introduced by therapeutic agents, such as cisplatin and araC, therefore reduce the activity of these compounds. In this study, the potential relationships between the lesion bypass Y-family DNA polymerases n, i and k (pol n, pol i, and pol k) and T-araC were examined. Biochemical studies indicated that the triphosphate metabolite of T-araC is a less preferred substrate for the Y-family polymerases. In addition, cell viability study indicated that pol n. deficient human fibroblast cells were more sensitive to T-araC when compared with the normal human fibroblast cells. Together, these results suggest that bypass polymerases reduced cell sensitivity to T-araC through helping cells to overcome the DNA damages introduced by T-araC.",
keywords = "araC, Bypass polymerases, Nucleoside analogs",
author = "Chen, {Yih Wen} and Chou, {Kai Ming}",
year = "2011",
language = "English (US)",
volume = "2",
pages = "340--346",
journal = "International Journal of Biochemistry and Molecular Biology",
issn = "2152-4114",
publisher = "e-Century Publishing Corporation",
number = "4",

}

TY - JOUR

T1 - DNA lesion bypass polymerases and 4'-thio-β-D-arabinofuranosylcytosine (T-arac)

AU - Chen, Yih Wen

AU - Chou, Kai Ming

PY - 2011

Y1 - 2011

N2 - The 4'-thio-(3-D-arabinofuranosylcytosine (T-araC) is a newly developed nucleoside analog that has shown promising activity against a broad spectrum of human solid tumors in both cellular and xenograft mice models. T-araC shares similar structure with another anticancer deoxycytidine analog, (3-D-arabinofuranosylcytosine (araC, cyta-rabine), which has been used in clinics for the treatment of acute myelogenous leukemia but has a very limited efficacy against solid tumors T-araC exerts its anticancer activity mainly by inhibiting replicative DNA polymerases from further extension after its incorporation into DNA. DNA lesion bypass polymerases can manage the DNA lesions introduced by therapeutic agents, such as cisplatin and araC, therefore reduce the activity of these compounds. In this study, the potential relationships between the lesion bypass Y-family DNA polymerases n, i and k (pol n, pol i, and pol k) and T-araC were examined. Biochemical studies indicated that the triphosphate metabolite of T-araC is a less preferred substrate for the Y-family polymerases. In addition, cell viability study indicated that pol n. deficient human fibroblast cells were more sensitive to T-araC when compared with the normal human fibroblast cells. Together, these results suggest that bypass polymerases reduced cell sensitivity to T-araC through helping cells to overcome the DNA damages introduced by T-araC.

AB - The 4'-thio-(3-D-arabinofuranosylcytosine (T-araC) is a newly developed nucleoside analog that has shown promising activity against a broad spectrum of human solid tumors in both cellular and xenograft mice models. T-araC shares similar structure with another anticancer deoxycytidine analog, (3-D-arabinofuranosylcytosine (araC, cyta-rabine), which has been used in clinics for the treatment of acute myelogenous leukemia but has a very limited efficacy against solid tumors T-araC exerts its anticancer activity mainly by inhibiting replicative DNA polymerases from further extension after its incorporation into DNA. DNA lesion bypass polymerases can manage the DNA lesions introduced by therapeutic agents, such as cisplatin and araC, therefore reduce the activity of these compounds. In this study, the potential relationships between the lesion bypass Y-family DNA polymerases n, i and k (pol n, pol i, and pol k) and T-araC were examined. Biochemical studies indicated that the triphosphate metabolite of T-araC is a less preferred substrate for the Y-family polymerases. In addition, cell viability study indicated that pol n. deficient human fibroblast cells were more sensitive to T-araC when compared with the normal human fibroblast cells. Together, these results suggest that bypass polymerases reduced cell sensitivity to T-araC through helping cells to overcome the DNA damages introduced by T-araC.

KW - araC

KW - Bypass polymerases

KW - Nucleoside analogs

UR - http://www.scopus.com/inward/record.url?scp=84862909276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862909276&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:84862909276

VL - 2

SP - 340

EP - 346

JO - International Journal of Biochemistry and Molecular Biology

JF - International Journal of Biochemistry and Molecular Biology

SN - 2152-4114

IS - 4

ER -