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Title: Regulation and disregulation of mammalian nucleotide excision repair: A pathway to nongermline breast carcinogenesis

Abstract

Nucleotide excision repair (NER) is important as a modulator of disease, especially in constitutive deficiencies, such as the cancer predisposition syndrome Xeroderma pigmentosum. We have found profound variation of NER capacity among normal individuals, between cell-types and during carcinogenesis. NER is a repair system for many types of DNA damage, and therefore many types of genotoxic carcinogenic exposures, including ultraviolet light, products of organic combustion, metals, oxidative stress, etc. Since NER is intimately related to cellular metabolism, requiring components of both the DNA replicative and transcription machinery, it has a narrow range of functional viability. Thus, genes in the NER pathway are expressed at the low levels manifested by, for example, nuclear transcription factors. Since NER activity and gene expression vary by cell-type, it is inherently epigenetically regulated. Furthermore, this epigenetic regulation is disregulated during sporadic breast carcinogenesis. Loss of NER is one basis of genomic instability, a required element in cellular transformation, and one that potentially modulates response to therapy. In this article, we demonstrate differences in NER capacity in eight adult mouse tissues, and place this result into the context of our previous work on mouse extraembryonic tissues, normal human tissues and sporadic early stage human breast cancer.

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. Nova Southeastern Univ., Fort Lauderdale, FL (United States)
Publication Date:
Research Org.:
Nova Southeastern Univ., Fort Lauderdale, FL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1344921
Grant/Contract Number:  
AC03-76SF01012
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Photochemistry and Photobiology
Additional Journal Information:
Journal Volume: 91; Journal Issue: 2; Journal ID: ISSN 0031-8655
Publisher:
The American Society of Photobiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Latimer, Jean J., Majekwana, Vongai J., Pabon-Padin, Yashira R., Pimpley, Manasi R., and Grant, Stephen G. Regulation and disregulation of mammalian nucleotide excision repair: A pathway to nongermline breast carcinogenesis. United States: N. p., 2014. Web. doi:10.1111/php.12387.
Latimer, Jean J., Majekwana, Vongai J., Pabon-Padin, Yashira R., Pimpley, Manasi R., & Grant, Stephen G. Regulation and disregulation of mammalian nucleotide excision repair: A pathway to nongermline breast carcinogenesis. United States. doi:10.1111/php.12387.
Latimer, Jean J., Majekwana, Vongai J., Pabon-Padin, Yashira R., Pimpley, Manasi R., and Grant, Stephen G. Fri . "Regulation and disregulation of mammalian nucleotide excision repair: A pathway to nongermline breast carcinogenesis". United States. doi:10.1111/php.12387. https://www.osti.gov/servlets/purl/1344921.
@article{osti_1344921,
title = {Regulation and disregulation of mammalian nucleotide excision repair: A pathway to nongermline breast carcinogenesis},
author = {Latimer, Jean J. and Majekwana, Vongai J. and Pabon-Padin, Yashira R. and Pimpley, Manasi R. and Grant, Stephen G.},
abstractNote = {Nucleotide excision repair (NER) is important as a modulator of disease, especially in constitutive deficiencies, such as the cancer predisposition syndrome Xeroderma pigmentosum. We have found profound variation of NER capacity among normal individuals, between cell-types and during carcinogenesis. NER is a repair system for many types of DNA damage, and therefore many types of genotoxic carcinogenic exposures, including ultraviolet light, products of organic combustion, metals, oxidative stress, etc. Since NER is intimately related to cellular metabolism, requiring components of both the DNA replicative and transcription machinery, it has a narrow range of functional viability. Thus, genes in the NER pathway are expressed at the low levels manifested by, for example, nuclear transcription factors. Since NER activity and gene expression vary by cell-type, it is inherently epigenetically regulated. Furthermore, this epigenetic regulation is disregulated during sporadic breast carcinogenesis. Loss of NER is one basis of genomic instability, a required element in cellular transformation, and one that potentially modulates response to therapy. In this article, we demonstrate differences in NER capacity in eight adult mouse tissues, and place this result into the context of our previous work on mouse extraembryonic tissues, normal human tissues and sporadic early stage human breast cancer.},
doi = {10.1111/php.12387},
journal = {Photochemistry and Photobiology},
issn = {0031-8655},
number = 2,
volume = 91,
place = {United States},
year = {2014},
month = {12}
}

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Works referenced in this record:

Repair Replication, Unscheduled DNA Synthesis, and the Repair of Mammalian DNA
journal, March 1969

  • Painter, R. B.; Cleaver, J. E.
  • Radiation Research, Vol. 37, Issue 3
  • DOI: 10.2307/3572686

Defective Repair Replication of DNA in Xeroderma Pigmentosum
journal, May 1968


Chemically-induced unscheduled DNA synthesis in primary rat hepatocyte cultures: A comparison with bacterial mutagenicity using 218 compounds
journal, January 1981

  • Probst, Gregory S.; McMahon, Robert E.; Hill, L. E.
  • Environmental Mutagenesis, Vol. 3, Issue 1
  • DOI: 10.1002/em.2860030103

Structure-activity relationships in the rat hepatocyte DNA-repair test for 300 chemicals
journal, November 1989

  • Williams, Gary M.; Mori, Hideki; McQueen, Charlene A.
  • Mutation Research/Reviews in Genetic Toxicology, Vol. 221, Issue 3
  • DOI: 10.1016/0165-1110(89)90039-0

The Comet Assay as a Repair Test for Prenatal Diagnosis of Xeroderma Pigmentosum and Trichothiodystrophy
journal, February 1997

  • Alapetite, Claire; Benoit, Annie; Moustacchi, Ethel
  • Journal of Investigative Dermatology, Vol. 108, Issue 2
  • DOI: 10.1111/1523-1747.ep12332692

Immunoprecipitation of Pyrimidine(6-4)pyrimidone Photoproducts and Cyclobutane Pyrimidine Dimers in uv-Irradiated DNA
journal, September 1990

  • Mitchell, David L.; Allison, James P.; Nairn, Rodney S.
  • Radiation Research, Vol. 123, Issue 3
  • DOI: 10.2307/3577736

A new flow cytometric method to follow DNA gap filling during nucleotide excision repair of UVc-induced damage
journal, January 2001


A rapid non-radioactive technique for measurement of repair synthesis in primary human fibroblasts by incorporation of ethynyl deoxyuridine (EdU)
journal, December 2008

  • Limsirichaikul, S.; Niimi, A.; Fawcett, H.
  • Nucleic Acids Research, Vol. 37, Issue 4
  • DOI: 10.1093/nar/gkp023

Elevated DNA Excision Repair Capacity in the Extraembryonic Mesoderm of the Midgestation Mouse Embryo
journal, October 1996

  • Latimer, J. J.; Hultner, M. L.; Cleaver, J. E.
  • Experimental Cell Research, Vol. 228, Issue 1
  • DOI: 10.1006/excr.1996.0294

Unique tissue-specific level of DNA nucleotide excision repair in primary human mammary epithelial cultures
journal, November 2003


Cell-type-specific level of DNA nucleotide excision repair in primary human mammary and ovarian epithelial cell cultures
journal, June 2008

  • Latimer, Jean J.; Johnson, Jennifer M.; Miles, Tiffany D.
  • Cell and Tissue Research, Vol. 333, Issue 3
  • DOI: 10.1007/s00441-008-0645-1

Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours
journal, March 1999


Nucleotide excision repair and its interplay with transcription
journal, November 2003


A method for detecting genetic toxicity using the RNA synthesis response to DNA damage
journal, January 2011

  • Morita, Yoko; Iwai, Shigenori; Kuraoka, Isao
  • The Journal of Toxicological Sciences, Vol. 36, Issue 5
  • DOI: 10.2131/jts.36.515

Damage recognition in nucleotide excision repair of DNA
journal, January 2000


Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects
journal, January 2008

  • Fousteri, Maria; Mullenders, Leon HF
  • Cell Research, Vol. 18, Issue 1
  • DOI: 10.1038/cr.2008.6

DNA repair diseases: what do they tell us about cancer and aging?
journal, January 2014


Identification of mismatch repair genes and their role in the development of cancer
journal, June 1995


DNA Repair in Mammalian Cells: Base excision repair: the long and short of it
journal, January 2009

  • Robertson, A. B.; Klungland, A.; Rognes, T.
  • Cellular and Molecular Life Sciences, Vol. 66, Issue 6
  • DOI: 10.1007/s00018-009-8736-z

Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair
journal, November 2010

  • Bradford, P. T.; Goldstein, A. M.; Tamura, D.
  • Journal of Medical Genetics, Vol. 48, Issue 3
  • DOI: 10.1136/jmg.2010.083022

The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)
journal, January 2013

  • Lai, Jin-Ping; Liu, Yen-Chun; Alimchandani, Meghna
  • Acta Neuropathologica Communications, Vol. 1, Issue 1
  • DOI: 10.1186/2051-5960-1-4

Spontaneous liver tumors and Benzo[a]pyrene-induced lymphomas in XPA-deficient mice
journal, May 1997


DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis
journal, December 1999


Correlation Between Deoxyribonucleic Acid Excision-Repair and Life-Span in a Number of Mammalian Species
journal, June 1974

  • Hart, R. W.; Setlow, R. B.
  • Proceedings of the National Academy of Sciences, Vol. 71, Issue 6
  • DOI: 10.1073/pnas.71.6.2169

Sensitive determination of pyrimidine dimers in DNA of UV-irradiated mammalian cells Introduction of T4 endonuclease V into frozen and thawed cells
journal, June 1981

  • van Zeeland, A. A.; Smith, Charles Allen; Hanawalt, Philip C.
  • Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 82, Issue 1
  • DOI: 10.1016/0027-5107(81)90148-2

p53 Binds and Activates the Xeroderma Pigmentosum DDB2 Gene in Humans but Not Mice
journal, May 2002


The effect of donor age on the processing of UV-damaged DNA by cultured human cells: Reduced DNA repair capacity and increased DNA mutability
journal, October 1996


Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA
journal, September 1995

  • Vries, Annemieke de; van Oostrom, Conny Th. M.; Hofhuis, Frans M. A.
  • Nature, Vol. 377, Issue 6545
  • DOI: 10.1038/377169a0

Nucleotide excision repair rates in rat tissues: Nucleotide excision repair rates in rat tissues
journal, March 2003


Cancer statistics, 2013
journal, January 2013

  • Siegel, Rebecca; Naishadham, Deepa; Jemal, Ahmedin
  • CA: A Cancer Journal for Clinicians, Vol. 63, Issue 1
  • DOI: 10.3322/caac.21166

Nucleotide excision repair and neurological diseases
journal, July 2008


Structure and function of the blood–brain barrier
journal, January 2010

  • Abbott, N. Joan; Patabendige, Adjanie A. K.; Dolman, Diana E. M.
  • Neurobiology of Disease, Vol. 37, Issue 1
  • DOI: 10.1016/j.nbd.2009.07.030

In vitro repair of oxidative DNA damage by human nucleotide excision repair system: Possible explanation for neurodegeneration in Xeroderma pigmentosum patients
journal, August 1997

  • Reardon, J. T.; Bessho, T.; Kung, H. C.
  • Proceedings of the National Academy of Sciences, Vol. 94, Issue 17
  • DOI: 10.1073/pnas.94.17.9463

Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
journal, October 1997


UV-induced DNA damage and repair: a review
journal, March 2002

  • Sinha, Rajeshwar P.; Häder, Donat-P.
  • Photochemical & Photobiological Sciences, Vol. 1, Issue 4
  • DOI: 10.1039/b201230h

Cell cycle checkpoints, DNA repair and DNA replication strategies
journal, January 1994


Nucleotide excision repair deficiency is intrinsic in sporadic stage I breast cancer
journal, November 2010

  • Latimer, J. J.; Johnson, J. M.; Kelly, C. M.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 50
  • DOI: 10.1073/pnas.0914772107

Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans
journal, January 1999

  • Hellerstein, M.; Hanley, M. B.; Cesar, D.
  • Nature Medicine, Vol. 5, Issue 1
  • DOI: 10.1038/4772

Haploinsufficiency for BRCA1is associated with normal levels of DNA nucleotide excision repair in breast tissue and blood lymphocytes
journal, June 2005

  • Latimer, Jean J.; Rubinstein, Wendy S.; Johnson, Jennifer M.
  • BMC Medical Genetics, Vol. 6, Issue 1
  • DOI: 10.1186/1471-2350-6-26

DNA double strand break repair in mammalian cells
journal, April 2000


Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells
journal, October 2011

  • Konishi, H.; Mohseni, M.; Tamaki, A.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 43
  • DOI: 10.1073/pnas.1110969108

Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology
journal, January 2008

  • Shuck, Sarah C.; Short, Emily A.; Turchi, John J.
  • Cell Research, Vol. 18, Issue 1
  • DOI: 10.1038/cr.2008.2

First Reported Patient with Human ERCC1 Deficiency Has Cerebro-Oculo-Facio-Skeletal Syndrome with a Mild Defect in Nucleotide Excision Repair and Severe Developmental Failure
journal, March 2007

  • Jaspers, Nicolaas G. J.; Raams, Anja; Silengo, Margherita Cirillo
  • The American Journal of Human Genetics, Vol. 80, Issue 3
  • DOI: 10.1086/512486

Nucleotide excision repair and human syndromes
journal, March 2000


Xeroderma Pigmentosum p48 Gene Enhances Global Genomic Repair and Suppresses UV-Induced Mutagenesis
journal, April 2000


Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage
journal, August 2014

  • Cleaver, James E.; Brennan-Minnella, Angela M.; Swanson, Raymond A.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 37
  • DOI: 10.1073/pnas.1414135111

Mitochondrial involvement in neurodegenerative diseases
journal, January 2013

  • Zsurka, Gábor; Kunz, Wolfram S.
  • IUBMB Life, Vol. 65, Issue 3
  • DOI: 10.1002/iub.1126

    Works referencing / citing this record:

    Nucleotide excision repair is a predictor of early relapse in pediatric acute lymphoblastic leukemia
    journal, October 2018

    • Ibrahim, Omar M.; As Sobeai, Homood M.; Grant, Stephen G.
    • BMC Medical Genomics, Vol. 11, Issue 1
    • DOI: 10.1186/s12920-018-0422-2