Nm23-H1 is responsible for SUMO-2-involved DNA synthesis induction after X-ray irradiation in human cells
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Published on: February 9, 2024
Wen-Zhi Guo1, Shigeru Sugaya, Mamoru Satoh
1Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
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.
Insights
X-ray irradiation increases DNA synthesis in human cells by reducing small ubiquitin-like protein modifier (SUMO-2). This involves decreased Nm23-H1 protein, leading to enhanced DNA synthesis and PCNA expression.
Area of Science:
- Molecular biology
- Cellular biology
- Radiation biology
Background:
- Nevoid basal cell carcinoma syndrome (NBCCS) cells exhibit increased DNA synthesis post-irradiation, linked to reduced small ubiquitin-like protein modifier (SUMO-2).
- SUMO-2 (SMT-3A) plays a role in cellular response to DNA damage.
Purpose of the Study:
- To investigate the role of SUMO-2 and its associated proteins in DNA synthesis induction after X-ray irradiation.
- To identify proteins affected by SUMO-2 reduction and their impact on DNA repair pathways.
Main Methods:
- siRNA-mediated knockdown of SUMO-2 in HeLa cells.
- Comparative proteomic analysis using 2D electrophoresis and mass spectrometry.
- Assessment of DNA synthesis activity, Nm23-H1 expression, and proliferating cell nuclear antigen (PCNA) levels post-irradiation.
Main Results:
- SUMO-2 reduction by siRNA in HeLa cells increased DNA synthesis activity after X-ray irradiation.
- Nm23-H1 (nucleoside diphosphate kinase) levels decreased post-irradiation in SUMO-2 depleted cells.
- Nm23-H1 depletion also induced DNA synthesis, and increased PCNA expression was observed, with Nm23-H1 showing SUMO-2 modification after irradiation.
Conclusions:
- Reduced Nm23-H1, potentially due to decreased sumoylation, is implicated in DNA synthesis induction following X-ray irradiation.
- The pathway involves the regulation of PCNA expression, highlighting a novel mechanism in DNA damage response.
