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 language | English |
|---|---|
| Pages (from-to) | 141-158 |
| Number of pages | 18 |
| Journal | International Journal of Molecular Sciences |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 23 2013 |
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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 journal › Article
}
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
C2 - 24366067
AN - SCOPUS:84891107898
VL - 15
SP - 141
EP - 158
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 1
ER -