title: Paraspeckle protein 1 (PSPC1) is involved in the cisplatin induced DNA damage response--role in G1/S checkpoint.
abstract: Paraspeckle protein 1 (PSPC1) was first identified as a structural protein of the subnuclear structure termed paraspeckle. However, the exact physiological functions of PSPC1 are still largely unknown. Previously, using a proteomic approach, we have shown that exposure to cisplatin can induce PSPC1 expression in HeLa cells, indicating the possible involvement for PSPC1 in the DNA damage response (DDR). In the current study, the role of PSPC1 in DDR was examined. First, it was found that cisplatin treatment could indeed induce the expression of PSPC1 protein. Abolishing PSPC1 expression by siRNA significantly inhibited cell growth, caused spontaneous cell death, and increased DNA damage. However, PSPC1 did not co-localize with γH2AX, 53BP1, or Rad51, indicating no direct involvement in DNA repair pathways mediated by these molecules. Interestingly, knockdown of PSPC1 disrupted the normal cell cycle distribution, with more cells entering the G2/M phase. Furthermore, while cisplatin induced G1/S arrest in HeLa cells, knockdown of PSPC1 caused cells to escape the G1/S checkpoint and enter mitosis, and resulted in more cell death. Taken together, these observations indicate a new role for PSPC1 in maintaining genome integrity during the DDR, particularly in the G1/S checkpoint.
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Xiangjing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of preventative medicine, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Kong
authors.affiliation: Lishui People's Hospital, Lishui, Zhejiang, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Chi
authors.affiliation: Center Testing International Corporation, Shenzhen, Guangdong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Chunlan
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Basic Science, Loma Linda University School of Medicine, Loma Linda, Californina, United States of America.
authors.forename: Penelope
authors.initials: P
authors.lastname: Duerksen-Hughes
authors.affiliation: Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Department of Toxicology, Hangzhou Normal University School of Public Health, Hangzhou, Zhejiang, China; Department of Biomedicine, College of Biotechnology, Zhejiang Agriculture and Forestry University, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D009687:Nuclear Proteins; C450059:PSPC1 protein, human; D016601:RNA-Binding Proteins; D002945:Cisplatin