The Mus101 family of chromosomal proteins, identified initially in Drosophila, is widely conserved and has been shown to function in a variety of DNA metabolic processes. Such functions include DNA replication, DNA damage repair, postreplication repair, damage checkpoint activation, chromosome stability, and chromosome condensation. Despite its conservation and widespread involvement in chromosome biogenesis, very little is known about how Mus101 is regulated and what other proteins are required for Mus101 to exert its functions. To learn more about Mus101, we have initiated an analysis of the protein in C. elegans. Here, we show that C. elegans mus-101 is an essential gene, that it is required for DNA replication, and that it also plays an important role in the DNA damage response. Furthermore, we use RNA interference (RNAi)-mediated reverse genetics to screen for genes that modify a mus-101 partial loss-of-function RNAi phenotype. Using a systematic approach toward modifier gene discovery, we have found five chromosome I genes that modify the mus-101 RNAi phenotype, and we go on to show that one of them encodes an E3 SUMO ligase that promotes SUMO modification of MUS-101 in vitro. These results expand our understanding of MUS-101 regulation and show that genetic interactions can be uncovered using screening strategies that rely solely on RNAi.

Purpose To report the association of X-inked ichthyosis and pre-Descemet corneal dystrophy with a deletion of the steroid sulfatase gene (STS) detected with microarray-based comparative genomic hybridization (aCGH). Methods A slit lamp biomicroscopic and cutaneous examination were performed, after which a saliva sample was collected as a source of genomic DNA. PCR amplification of each of the 10 exons of STS was performed, as was aCGH on genomic DNA to detect copy number variation (CNV). Results Slit lamp examination revealed punctate opacities in the posterior corneal stroma of each eye. Cutaneous examination demonstrated scaling and flaking skin of the arms and legs. PCR amplification using primers designed to amplify each of the 10 exons of STS failed to produce any amplicons. Subsequently, aCGH performed on genomic DNA revealed a microdeletion in the Xp22.31 cytoband of approximately 1.7 megabases, containing STS. Conclusions The identification of a microdeletion within Xp22.3 containing STS with aCGH in an individual with suspected pre-Descemet corneal dystrophy and X-inked ichthyosis demonstrates the clinical utility of CNV analysis in confirming a presumptive clinical diagnosis.