title: CTT1 overexpression increases the replicative lifespan of MMS-sensitive Saccharomyces cerevisiae deficient in KSP1.
abstract: Ksplp is a nuclear-localized Ser/Thr kinase that is not essential for the vegetative growth of yeast. A global gene function analysis in yeast suggested that Ksplp was involved in the oxidative stress response; however, the underlying mechanism remains unclear. Here, we showed that KSP1-deficient yeast cells exhibit hypersensitivity to the DNA alkylating agent methyl methanesulphonate (MMS), and treatment of the KSP1-deficient strain with MMS could trigger abnormal mitochondrial membrane potential and up-regulate reactive oxygen species (ROS) production. In addition, the mRNA expression level of the catalase gene CTT1 (which encodes cytosolic catalase) and total catalase activity were strongly down-regulated in the KSP1-deleted strain compared with those in wild-type cells. Moreover, the KSP1 deficiency also leads to a shortened replicative lifespan, which could be restored by the increased expression of CTT1. On the other hand, KSP1-overexpressed (KSP1OX) yeast cells exhibited increased resistance towards MMS, an effect that was, at least in part, CTT1 independent. Collectively, these findings highlight the involvement of Ksplp in the DNA damage response and implicate Ksplp as a modulator of the replicative lifespan.
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808, China.
authors.forename: Hua-Zhen
authors.initials: HZ
authors.lastname: Zheng
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Institute of Gynecology, Women and Children's Hospital of Guangdong Province, Guangzhou 511442, China.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Hong
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808, China.
authors.forename: Hong-Jing
authors.initials: HJ
authors.lastname: Cui
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808, China.
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Jiang
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808, China.
authors.forename: Hui-Ji
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Zhong-Jun
authors.initials: ZJ
authors.lastname: Zhou
authors.affiliation: Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808, China; Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Dongguan 523808, China. Electronic address: xgliu@gdmu.edu.cn.
authors.forename: Xin-Guang
authors.initials: XG
authors.lastname: Liu
mesh_terms: D002374:Catalase / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D002374:Catalase; C534961:Ksp1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases
keywords: CTT1; KSP1; MMS; Replicative lifespan