title: A novelPOLHmutation causes XP-V disease and XP-V tumor proneness may involve imbalance of numerous DNA polymerases.
abstract: Xeroderma pigmentosum variant (XP-V) is a subtype of xeroderma pigmentosum (XP) disease with typical pigmentation and types of cancer in the oral maxillofacial and other sun-exposed regions. Few factors of tumor proneness in XP-V have been completely elucidated with the exception of thePOLH[which encodes DNA polymerase η (pol η)] mutation. The aim of the present study was to identify thePOLHmutation in an XP-V patient and to explore the roles of specific additional polymerases in XP-V tumor proneness. ThePOLHgene was sequenced in the patient and the expression of pol η, ι, κ, θ and ζ was tested in XP-V tumor cells and cell lines, as well as in HeLa cells withPOLHknockdown. The results revealed a novel, large homozygous deletion ofPOLH(del exon 5-9) in the patient. Lower expression of pol κ, θ and ζ were observed in the XP-V cells and similar changes were observed in HeLa cells withPOLHknockdown. Consistent with XP-V tumor cells, following UV irradiation, the expression of pol κ and θ presented was significantly increased in the XP-V cell lines compared with that in the normal control cells. The unusual expression of other polymerases, besides pol η, identified in the present study indicated that these polymerases may also be key in XP-V cells genetic instability, which accelerates tumor formation.
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Guilan
authors.initials: G
authors.lastname: Zhou
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Yaling
authors.initials: Y
authors.lastname: Song
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Bian
keywords: POLH; XP-V; Xeroderma pigmentosum; mutation