c 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 ϳ1,500 transcripts, with DNA replication and repair genes being highly enriched among those with reduced expression. Splicing defects were evident in ϳ750 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. Proper repair of DNA damage is crucial for the maintenance of genomic integrity. DNA is constantly bombarded by genotoxic factors, leading to the acquisition of multiple types of DNA damage, including oxidation and alkylation of bases, DNA crosslinking, formation of pyrimidine dimers, adduct formation, and DNA breaks.Damage encountered during DNA replication is especially problematic, and cells possess tightly regulated mechanisms to ensure that DNA is replicated completely and accurately to maintain genomic integrity. The ataxia telangiectasia-mutated and Rad3-related (ATR) signaling pathway is a major mechanism by which cells respond to and repair replication-associated damage (1). DNA damage encountered by the replication machinery leads to replication fork stalling and/or collapse (2, 3). This is often accompanied by uncoupling of the DNA polymerase from the replicative helicase that unwinds the DNA at the fork, leading to the formation of single-stranded DNA (ssDNA) (1, 4). The ssDNA is then coated by replication protein A (RPA), followed by the binding of ATRIP to RPA, which recruits its binding partner ATR to the stalled replication fork (5-7). The RFC-RAD17 complex, the RAD9-RAD1-HUS1 (9-1-1) complex, and TOPBP1 are also recruited, contributing to the activation of ATR (1, 8, 9). Additional mechanisms operate to fine-tune ATR regulation (10). Once ATR is activated, it phosphorylates CHK1 and hundreds of other proteins, affecting a phosphorylation cascade that results in the activation of cell cycle checkpoints, stabilization of the replication fork, and repair of the DNA damage (1, 11).Here we describe the function of Enhancer of Rudimentary Homolog (ERH), which we identified by a whole-genome small interfering RNA (siRNA) screen designed to find replication stress response genes. ERH is the homolog of the Drosophila melanogaster E(r) gene, which was found as an enhancer of the phenotype caused by mutations in ...

Despite being a short-lived, extraembryonic tissue, the amnioserosa plays critical roles in the major morphogenetic events of Drosophila embryogenesis. These roles involve both cellular mechanics and biochemical signaling. Its best-known role is in dorsal closure-well studied by both developmental biologists and biophysicists-but the amnioserosa is also important during earlier developmental stages. Here, we provide an overview of amnioserosa specification and its role in several key developmental stages: germ band extension, germ band retraction, and dorsal closure. We also compare embryonic development in Drosophila and its relative Megaselia to highlight how the amnioserosa and its roles have evolved. Placed in context, the amnioserosa provides a fascinating example of how signaling, mechanics, and morphogen patterns govern cell-type specification and subsequent morphogenetic changes in cell shape, orientation, and movement. Developmental Dynamics 245:558-568,