The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells

Chih Wei Chen, Ning Tsao, Lin Yi Huang, Yun Yen, Xiyong Liu, Christine Lehman, Yuh Hwa Wang, Mei Chun Tseng, Yu Ju Chen, Yi Chi Ho, Chian Feng Chen, Zee Fen Chang

研究成果: 雜誌貢獻文章

7 引文 (Scopus)

摘要

The appropriate supply of dNTPs is critical for cell growth and genome integrity. Here, we investigated the interrelationship between dUTP pyrophosphatase (dUTPase) and ribonucleotide reductase (RNR) in the regulation of genome stability. Our results demonstrate that reducing the expression of dUTPase increases genome stress in cancer. Analysis of clinical samples reveals a significant correlation between the combination of low dUTPase and high R2, a subunit of RNR, and a poor prognosis in colorectal and breast cancer patients. Furthermore, overexpression of R2 in non-tumorigenic cells progressively increases genome stress, promoting transformation. These cells display alterations in replication fork progression, elevated genomic uracil, and breaks at AT-rich common fragile sites. Consistently, overexpression of dUTPase abolishes R2-induced genome instability. Thus, the expression level of dUTPase determines the role of high R2 in driving genome instability in cancer cells.
原文英語
頁(從 - 到)1287-1299
頁數13
期刊Cell Reports
16
發行號5
DOIs
出版狀態已發佈 - 八月 2 2016

指紋

Ribonucleotide Reductases
Genomic Instability
Genes
Cells
Genome
Neoplasms
Uracil
Cell growth
Colorectal Neoplasms
dUTP pyrophosphatase
Breast Neoplasms
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

引用此文

Chen, C. W., Tsao, N., Huang, L. Y., Yen, Y., Liu, X., Lehman, C., ... Chang, Z. F. (2016). The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells. Cell Reports, 16(5), 1287-1299. https://doi.org/10.1016/j.celrep.2016.06.094

The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells. / Chen, Chih Wei; Tsao, Ning; Huang, Lin Yi; Yen, Yun; Liu, Xiyong; Lehman, Christine; Wang, Yuh Hwa; Tseng, Mei Chun; Chen, Yu Ju; Ho, Yi Chi; Chen, Chian Feng; Chang, Zee Fen.

於: Cell Reports, 卷 16, 編號 5, 02.08.2016, p. 1287-1299.

研究成果: 雜誌貢獻文章

Chen, CW, Tsao, N, Huang, LY, Yen, Y, Liu, X, Lehman, C, Wang, YH, Tseng, MC, Chen, YJ, Ho, YC, Chen, CF & Chang, ZF 2016, 'The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells', Cell Reports, 卷 16, 編號 5, 頁 1287-1299. https://doi.org/10.1016/j.celrep.2016.06.094
Chen, Chih Wei ; Tsao, Ning ; Huang, Lin Yi ; Yen, Yun ; Liu, Xiyong ; Lehman, Christine ; Wang, Yuh Hwa ; Tseng, Mei Chun ; Chen, Yu Ju ; Ho, Yi Chi ; Chen, Chian Feng ; Chang, Zee Fen. / The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells. 於: Cell Reports. 2016 ; 卷 16, 編號 5. 頁 1287-1299.
@article{2633b0d543394dc2af85aa711cff3f18,
title = "The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells",
abstract = "The appropriate supply of dNTPs is critical for cell growth and genome integrity. Here, we investigated the interrelationship between dUTP pyrophosphatase (dUTPase) and ribonucleotide reductase (RNR) in the regulation of genome stability. Our results demonstrate that reducing the expression of dUTPase increases genome stress in cancer. Analysis of clinical samples reveals a significant correlation between the combination of low dUTPase and high R2, a subunit of RNR, and a poor prognosis in colorectal and breast cancer patients. Furthermore, overexpression of R2 in non-tumorigenic cells progressively increases genome stress, promoting transformation. These cells display alterations in replication fork progression, elevated genomic uracil, and breaks at AT-rich common fragile sites. Consistently, overexpression of dUTPase abolishes R2-induced genome instability. Thus, the expression level of dUTPase determines the role of high R2 in driving genome instability in cancer cells.",
author = "Chen, {Chih Wei} and Ning Tsao and Huang, {Lin Yi} and Yun Yen and Xiyong Liu and Christine Lehman and Wang, {Yuh Hwa} and Tseng, {Mei Chun} and Chen, {Yu Ju} and Ho, {Yi Chi} and Chen, {Chian Feng} and Chang, {Zee Fen}",
year = "2016",
month = "8",
day = "2",
doi = "10.1016/j.celrep.2016.06.094",
language = "English",
volume = "16",
pages = "1287--1299",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells

AU - Chen, Chih Wei

AU - Tsao, Ning

AU - Huang, Lin Yi

AU - Yen, Yun

AU - Liu, Xiyong

AU - Lehman, Christine

AU - Wang, Yuh Hwa

AU - Tseng, Mei Chun

AU - Chen, Yu Ju

AU - Ho, Yi Chi

AU - Chen, Chian Feng

AU - Chang, Zee Fen

PY - 2016/8/2

Y1 - 2016/8/2

N2 - The appropriate supply of dNTPs is critical for cell growth and genome integrity. Here, we investigated the interrelationship between dUTP pyrophosphatase (dUTPase) and ribonucleotide reductase (RNR) in the regulation of genome stability. Our results demonstrate that reducing the expression of dUTPase increases genome stress in cancer. Analysis of clinical samples reveals a significant correlation between the combination of low dUTPase and high R2, a subunit of RNR, and a poor prognosis in colorectal and breast cancer patients. Furthermore, overexpression of R2 in non-tumorigenic cells progressively increases genome stress, promoting transformation. These cells display alterations in replication fork progression, elevated genomic uracil, and breaks at AT-rich common fragile sites. Consistently, overexpression of dUTPase abolishes R2-induced genome instability. Thus, the expression level of dUTPase determines the role of high R2 in driving genome instability in cancer cells.

AB - The appropriate supply of dNTPs is critical for cell growth and genome integrity. Here, we investigated the interrelationship between dUTP pyrophosphatase (dUTPase) and ribonucleotide reductase (RNR) in the regulation of genome stability. Our results demonstrate that reducing the expression of dUTPase increases genome stress in cancer. Analysis of clinical samples reveals a significant correlation between the combination of low dUTPase and high R2, a subunit of RNR, and a poor prognosis in colorectal and breast cancer patients. Furthermore, overexpression of R2 in non-tumorigenic cells progressively increases genome stress, promoting transformation. These cells display alterations in replication fork progression, elevated genomic uracil, and breaks at AT-rich common fragile sites. Consistently, overexpression of dUTPase abolishes R2-induced genome instability. Thus, the expression level of dUTPase determines the role of high R2 in driving genome instability in cancer cells.

UR - http://www.scopus.com/inward/record.url?scp=84989877205&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989877205&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.06.094

DO - 10.1016/j.celrep.2016.06.094

M3 - Article

VL - 16

SP - 1287

EP - 1299

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

ER -