Centro de Estudios Fotosintéticos y Bioquímicos, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
J Exp Bot. 2011 May;62(8):2925-37. doi: 10.1093/jxb/err001. Epub 2011 Feb 9.
Deleterious effects of UV-B radiation on DNA include the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). These lesions must be repaired to maintain the integrity of DNA and provide genetic stability. Of the several repair systems involved in the recognition and removal of UV-B-induced lesions in DNA, the focus in the present study was on the mismatch repair system (MMR). The contribution of MutSα (MSH2-MSH6) to UV-induced DNA lesion repair and cell cycle regulation was investigated. MSH2 and MSH6 genes in Arabidopsis and maize are up-regulated by UV-B, indicating that MMR may have a role in UV-B-induced DNA damage responses. Analysis of promoter sequences identified MSH6 as a target of the E2F transcription factors. Using electrophoretic mobility shift assays, MSH6 was experimentally validated as an E2F target gene, suggesting an interaction between MMR genes and the cell cycle control. Mutations in MSH2 or MSH6 caused an increased accumulation of CPDs relative to wild-type plants. In addition, msh2 mutant plants showed a different expression pattern of cell cycle marker genes after the UV-B treatment when compared with wild-type plants. Taken together, these data provide evidence that plant MutSα is involved in a UV-B-induced DNA damage response pathway.
UV-B 辐射对 DNA 的有害影响包括形成环丁烷嘧啶二聚体（CPDs）和嘧啶（6-4）嘧啶酮光产物（6-4PPs）。这些损伤必须修复以维持 DNA 的完整性并提供遗传稳定性。在涉及识别和去除 DNA 中 UV-B 诱导损伤的几种修复系统中，本研究的重点是错配修复系统（MMR）。研究了 MutSα（MSH2-MSH6）对 UV 诱导的 DNA 损伤修复和细胞周期调控的贡献。拟南芥和玉米中的 MSH2 和 MSH6 基因被 UV-B 上调，表明 MMR 可能在 UV-B 诱导的 DNA 损伤反应中发挥作用。对启动子序列的分析确定 MSH6 是 E2F 转录因子的靶标。通过电泳迁移率变动分析，实验验证了 MSH6 是 E2F 靶基因，表明 MMR 基因与细胞周期控制之间存在相互作用。MSH2 或 MSH6 的突变导致 CPDs 的积累相对于野生型植物增加。此外，与野生型植物相比，msh2 突变体植物在 UV-B 处理后细胞周期标记基因的表达模式不同。总之，这些数据提供了证据表明植物 MutSα 参与了 UV-B 诱导的 DNA 损伤反应途径。
