title: Loss of Smu1 function de-represses DNA replication and over-activates ATR-dependent replication checkpoint.
abstract: Smu1 is an evolutionarily conserved gene that encodes a member of the WD40-repeat protein family. Disruption of Smu1 function leads to multiple cellular defects including chromosomal instability, aberrant DNA replication and alternative RNA splicing events. In this paper, we show that Smu1 is a chromatin-bound protein that functions as a negative regulator of DNA replication. Knockdown of Smu1 gene expression promotes excessive incorporation of dNTP analogue, implicating the acceleration of DNA synthesis. Smu1-silenced cells show an excessive activation of replication checkpoint in response to ultraviolate (UV) or hydroxyurea treatment, indicating that abnormal stimulation of DNA replication leads to instability of genomic structure. Hence, we propose that Smu1 participates in the protection of genomic integrity by negatively regulating the process of DNA synthesis.
authors.affiliation: Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, PR China.
authors.forename: Laifeng
authors.initials: L
authors.lastname: Ren
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Liandi
authors.initials: L
authors.lastname: Guo
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Xin
authors.initials: X
authors.lastname: Shao
authors.forename: Chunlei
authors.initials: C
authors.lastname: Yang
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Tang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints; D057809:HEK293 Cells; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C583515:Smu1 protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D006918:Hydroxyurea