Enhancer of Rudimentary Homolog affects the replication stress response through regulation of RNA processing.
AUTHORS
- PMID: 26100022[PubMed].
ABSTRACT
Accurate replication of DNA is imperative for the maintenance of genomic integrity. We identified enhancer of rudimentary homolog (ERH) using a whole genome 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 approximately 1500 transcripts with DNA replication and repair genes being highly enriched amongst those with reduced expression. Splicing defects were evident in approximately 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.
Accurate replication of DNA is imperative for the maintenance of genomic integrity. We identified enhancer of rudimentary homolog (ERH) using a whole genome 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 approximately 1500 transcripts with DNA replication and repair genes being highly enriched amongst those with reduced expression. Splicing defects were evident in approximately 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.