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

Joyce T. Reardon, Tadayoshi Bessho, Hsiang Chuan Kung, Philip H. Bolton, Aziz Sancar

Research output: Contribution to journalArticle

299 Citations (Scopus)

Abstract

Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers caused by sunlight and, as a consequence, develop multiple cancers in areas exposed to light. The second most common sign, present in 20-30% of XP patients, is a set of neurological abnormalities caused by neuronal death in the central and peripheral nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so the cause of neurodegeneration in XP patients remains unexplained. In this study, we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol, are excised from DNA in vitro by the same enzyme system responsible for removing pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP neurological disease may be caused by defective repair of lesions that are produced in nerve cells by reactive oxygen species generated as by-products of an active oxidative metabolism.

Original languageEnglish (US)
Pages (from-to)9463-9468
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number17
DOIs
StatePublished - Aug 19 1997

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Xeroderma Pigmentosum
DNA Repair
DNA Damage
Pyrimidine Dimers
Sunlight
DNA Adducts
DNA
Peripheral Nervous System
Reactive Oxygen Species
Central Nervous System
Neurons
Light
In Vitro Techniques
Enzymes
Neoplasms

ASJC Scopus subject areas

  • General

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In vitro repair of oxidative DNA damage by human nucleotide excision repair system : Possible explanation for neurodegeneration in Xeroderma pigmentosum patients. / Reardon, Joyce T.; Bessho, Tadayoshi; Kung, Hsiang Chuan; Bolton, Philip H.; Sancar, Aziz.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 17, 19.08.1997, p. 9463-9468.

Research output: Contribution to journalArticle

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