This family contains the breast cancer tumour suppressor BRCA2-interacting protein DSS1 and its homologue SEM1, both of which are short acidic proteins. DSS1 has been shown to be a conserved component of the Rae1 mediated mRNA export pathway in Schizosaccharomyces pombe (PMID:15990877).
This family includes yeast Sem1 and its mammalian homologue, DSS1.
Sem1/DSS1 (also known as rpn15) is a component of lid subcomplex of 26S proteasome regulatory subunit [ (PUBMED:23643786) (PUBMED:24412063) (PUBMED:15117943) ]. Besides being a subunit of the 26S proteasome, Sem1/DSS1 associates with other protein complexes [ (PUBMED:26944332) ]. It is a component of the nuclear pore complex (NPC)-associated TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation [ (PUBMED:24896180) (PUBMED:19289793) (PUBMED:26456823) ].
Loss of DSS1 in humans has been associated with split hand/split foot malformations [ (PUBMED:8782053) ].
Homolog of BRCA2-interacting Dss1p and Uap56p link Mlo3p and Rae1p for mRNAexport in fission yeast.
EMBO J. 2005; 24: 2512-23
Display abstract
The breast cancer tumor suppressor BRCA2-interacting protein, DSS1, and itshomologs are critical for DNA recombination in eukaryotic cells. We found thatDss1p, along with Mlo3p and Uap56p, Schizosaccharomyces pombe homologs of twomessenger RNA (mRNA) export factors of the NXF-NXT pathway, is required for mRNA export in S. pombe. Previously, we showed that the nuclear pore-associated Rae1p is an essential mRNA export factor in S. pombe. Here, we show that Dss1p andUap56p function by linking mRNA adapter Mlo3p to Rae1p for targeting mRNA-proteincomplex (mRNP) to the proteins of the nuclear pore complex (NPC). Dss1ppreferentially recruits to genes in vivo and interacts with -FG (phenylalanineglycine) nucleoporins in vivo and in vitro. Thus, Dss1p may function at multiple steps of mRNA export, from mRNP biogenesis to their targeting and translocationthrough the NPC.
SEM1, a homologue of the split hand/split foot malformation candidate gene Dss1, regulates exocytosis and pseudohyphal differentiation in yeast.
Proc Natl Acad Sci U S A. 1999; 96: 909-14
Display abstract
The exocyst is an essential multiprotein complex mediating polarized secretion inyeast. Here we describe a gene, SEM1, that can multicopy-suppress exocyst mutantssec3-2, sec8-9, sec10-2, and sec15-1. SEM1 is highly conserved among eukaryoticspecies. Its human homologue, DSS1, has been suggested as a candidate gene forthe split hand/split foot malformation disorder. SEM1 is not an essential gene.However, its deletion rescued growth of the temperature-sensitive exocyst mutantssec3-2, sec8-9, sec10-1, and sec15-1 at the restrictive temperature. Cellfractionation showed that Sem1p is mainly cytosolic but also associates with the microsomal fraction. In linear sucrose gradients, Sem1p cosedimented with theexocyst component Sec8p. In diploid cells that normally do not form pseudohyphae (S288C background), deletion of SEM1 triggered pseudohyphal growth. Thisphenotype was abolished after reintroduction of either SEM1 or the mousehomologue Dss1 into the cells. In diploids that have normal capacity forpseudohyphal growth (Sigma1278b background), deletion of SEM1 enhancedfilamentous growth. The functionality of both SEM1 and Dss1 in a differentiation process in yeast suggests that Dss1 indeed could be the gene affected in thesplit hand/split foot malformation disorder. These results characterize SEM1 as aregulator of both exocyst function and pseudohyphal differentiation and suggest aunique link between these two cellular functions in yeast.
