title: Enhancer of Rudimentary Homolog Affects the Replication Stress Response through Regulation of RNA Processing.
abstract: Accurate replication of DNA is imperative for the maintenance of genomic integrity. We identified Enhancer of Rudimentary Homolog (ERH) using a whole-genome RNA interference (RNAi) screen to discover novel proteins that function in the replication stress response. Here we report that ERH is important for DNA replication and recovery from replication stress. ATR pathway activity is diminished in ERH-deficient cells. The reduction in ATR signaling corresponds to a decrease in the expression of multiple ATR pathway genes, including ATR itself. ERH interacts with multiple RNA processing complexes, including splicing regulators. Furthermore, splicing of ATR transcripts is deficient in ERH-depleted cells. Transcriptome-wide analysis indicates that ERH depletion affects the levels of ∼1,500 transcripts, with DNA replication and repair genes being highly enriched among those with reduced expression. Splicing defects were evident in ∼750 protein-coding genes, which again were enriched for DNA metabolism genes. Thus, ERH regulation of RNA processing is needed to ensure faithful DNA replication and repair.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Kavanaugh
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Runxiang
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Kareem N
authors.initials: KN
authors.lastname: Mohni
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Glick
authors.affiliation: Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Lacy
authors.affiliation: Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: M Shane
authors.initials: MS
authors.lastname: Hutson
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ascano
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA david.cortez@vanderbilt.edu.
authors.forename: David
authors.initials: D
authors.lastname: Cortez
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D034622:RNA Interference; D012326:RNA Splicing / Q000235:genetics*; D034741:RNA, Small Interfering; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C484495:ERH protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins