A human XPC protein interactome-A resource

Abigail Lubin, Ling Zhang, Hua Chen, Victoria M. White, Feng Gong

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening. Our screening showed 49 novel interactors of XPC involved in DNA repair and replication, proteolysis and post-translational modifications, transcription regulation, signal transduction, and metabolism. Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. This high-throughput characterization of the XPC interactome provides a resource for future exploration and suggests that XPC may have many uncharacterized cellular functions.

Original languageEnglish
Pages (from-to)141-158
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume15
Issue number1
DOIs
StatePublished - Dec 23 2013

Fingerprint

DNA Repair
Xeroderma Pigmentosum
resources
DNA
Repair
deoxyribonucleic acid
genome
nucleotides
Nucleotides
proteins
Proteins
Screening
screening
Genes
Throughput
Genome
Proteolysis
damage
Photosensitivity Disorders
pathogenesis

Keywords

  • Nucleotide excision repair
  • Xeroderma pigmentosum
  • XPC
  • Yeast two hybrid

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry

Cite this

A human XPC protein interactome-A resource. / Lubin, Abigail; Zhang, Ling; Chen, Hua; White, Victoria M.; Gong, Feng.

In: International Journal of Molecular Sciences, Vol. 15, No. 1, 23.12.2013, p. 141-158.

Research output: Contribution to journalArticle

Lubin, Abigail ; Zhang, Ling ; Chen, Hua ; White, Victoria M. ; Gong, Feng. / A human XPC protein interactome-A resource. In: International Journal of Molecular Sciences. 2013 ; Vol. 15, No. 1. pp. 141-158.
@article{07e31a3824e64cdb8ec1cb6040c8165a,
title = "A human XPC protein interactome-A resource",
abstract = "Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening. Our screening showed 49 novel interactors of XPC involved in DNA repair and replication, proteolysis and post-translational modifications, transcription regulation, signal transduction, and metabolism. Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. This high-throughput characterization of the XPC interactome provides a resource for future exploration and suggests that XPC may have many uncharacterized cellular functions.",
keywords = "Nucleotide excision repair, Xeroderma pigmentosum, XPC, Yeast two hybrid",
author = "Abigail Lubin and Ling Zhang and Hua Chen and White, {Victoria M.} and Feng Gong",
year = "2013",
month = "12",
day = "23",
doi = "10.3390/ijms15010141",
language = "English",
volume = "15",
pages = "141--158",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",

}

TY - JOUR

T1 - A human XPC protein interactome-A resource

AU - Lubin, Abigail

AU - Zhang, Ling

AU - Chen, Hua

AU - White, Victoria M.

AU - Gong, Feng

PY - 2013/12/23

Y1 - 2013/12/23

N2 - Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening. Our screening showed 49 novel interactors of XPC involved in DNA repair and replication, proteolysis and post-translational modifications, transcription regulation, signal transduction, and metabolism. Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. This high-throughput characterization of the XPC interactome provides a resource for future exploration and suggests that XPC may have many uncharacterized cellular functions.

AB - Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening. Our screening showed 49 novel interactors of XPC involved in DNA repair and replication, proteolysis and post-translational modifications, transcription regulation, signal transduction, and metabolism. Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. This high-throughput characterization of the XPC interactome provides a resource for future exploration and suggests that XPC may have many uncharacterized cellular functions.

KW - Nucleotide excision repair

KW - Xeroderma pigmentosum

KW - XPC

KW - Yeast two hybrid

UR - http://www.scopus.com/inward/record.url?scp=84891107898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891107898&partnerID=8YFLogxK

U2 - 10.3390/ijms15010141

DO - 10.3390/ijms15010141

M3 - Article

VL - 15

SP - 141

EP - 158

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

ER -