title: Nm23-H1 is responsible for SUMO-2-involved DNA synthesis induction after X-ray irradiation in human cells.
abstract: Human cells derived from nevoid basal carcinoma syndrome (NBCCS) patients show increased levels of DNA synthesis activity after X-ray irradiation which is suggested to be casually related to reduction in cellular amounts of small ubiquitin-like protein modifier (SUMO-2/SMT-3A). In the present study, an increased level of DNA synthesis activity was found 8h after X-ray irradiation in HeLa cells with reduction in SUMO-2 amounts by siRNA treatment for SUMO-2. When comparative proteomic analysis was performed between the siRNA and mimic control siRNA treated cells using two-dimensional (2D) electrophoresis and mass spectrometry, three proteins were identified as candidates. Our research focused on Nm23-H1, a nucleoside diphosphate kinase, whose amounts decreased after X-ray irradiation in HeLa cells treated with siRNA for SUMO-2. In the Nm23-H1 siRNA treated cells, induction of DNA synthesis was also detected. Furthermore, in synchronized HeLa cells, DNA synthesis was confirmed in the S phase. Moreover, increased expression of proliferating cell nuclear antigen (PCNA) was observed in Nm23-H1 siRNA treated HeLa cells after X-ray irradiation. In addition, Nm23-H1 was modified with SUMO-2 after X-ray irradiation. The present findings suggest that the reduction of Nm23-H1 is related to the decrease in sumoylation, which in turn, is involved in the induction of DNA synthesis via the regulation of PCNA expression after X-ray irradiation.
authors.affiliation: Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Guo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugaya
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.forename: Takaki
authors.initials: T
authors.lastname: Hiwasa
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kita
authors.forename: Nobuo
authors.initials: N
authors.lastname: Suzuki