In yeast, the differentiation process at the end of meiosis generates four daughter cells inside the boundaries of the mother cell. A meiosis-speci®c plaque (MP) at the spindle pole bodies (SPBs) serves as the starting site for the formation of the prospore membranes (PSMs) that are destined to encapsulate the post-meiotic nuclei. Here we report the identi®cation of Ady3p and Ssp1p, which are functional components of the leading edge protein (LEP) coat, that covers the ringshaped opening of the PSMs. Ssp1p is required for the assembly of the LEP coat, which consists of at least three proteins (Ssp1p, Ady3p and Don1p). The assembly of the LEP coat starts with the formation of cytosolic precursors, which then bind in an Ady3p-dependent manner to the SPBs. Subsequent processes at the SPBs leading to functional LEP coats require Ssp1p and the MP components. During growth of the PSMs, the LEP coat functions in formation of the cupshaped membrane structure that is indispensable for the regulated cellularization of the cytoplasm around the post-meiotic nuclei.

Intracellular budding is a developmentally regulated type of cell division common to many fungi and protists. In Saccaromyces cerevisiae, intracellular budding requires the de novo assembly of membranes, the prospore membranes (PSMs) and occurs during spore formation in meiosis. Ssp1p is a sporulation-specific protein that has previously been shown to localize to secretory vesicles and to recruit the leading edge protein coat (LEP coat) proteins to the opening of the PSM. Here, we show that Ssp1p is a multidomain protein with distinct domains important for PI(4,5)P 2 binding, binding to secretory vesicles and inhibition of vesicle fusion, interaction with LEP coat components and that it is subject to sumoylation and degradation. We found non-essential roles for Ssp1p on the level of vesicle transport and an essential function of Ssp1p to regulate the opening of the PSM. Together, our results indicate that Ssp1p has a domain architecture that resembles to some extent the septin class of proteins, and that the regulated removal of Ssp1p from the PSM is the major step underlying cytokinesis in yeast sporulation.

Epigenetic changes are important etiological factors of human cancer. Epigenetic information in chromatin (known as 'histone code') is a fascinating feature used by cells to extend and modulate the genetic (DNA) code. The histone code is thus proposed to be 'read' by cells to regulate accessibility to, and functions of, chromatin DNA. While the role of the epigenetic code involving chromatin modifying/remodeling complexes in transcriptional regulation is well established, it is only recently that these mechanisms have been implicated in DNA damage detection and DNA repair. However, how the components of the DNA damage sensing and repair machinery gain access to broken DNA in compacted chromatin remains a mystery. Recent studies provide important insights into DNA damage-and repair-specific modifications to histones and shed light on how the epigenetic code controls DNA repair.

The Wnt pathway is a key regulator of embryonic development and stem cell self-renewal, and hyperactivation of the Wnt signalling is associated with many human cancers. The central player in the Wnt pathway is β-catenin, a cytoplasmic protein whose function is tightly controlled by ubiquitination and degradation, however the precise regulation of β-catenin stability/degradation remains elusive. Here, we report a new mechanism of β-catenin ubiquitination acting in the context of chromatin. This mechanism is mediated by the histone acetyltransferase (HAT) complex component TRRAP and Skp1, an invariable component of the Skp-Cullin-F-box (SCF) ubiquitin ligase complex. TRRAP interacts with Skp1/SCF and mediates its recruitment to β-catenin target promoter in chromatin. TRRAP deletion leads to a reduced level of β-catenin ubiquitination, lower degradation rate and accumulation of β-catenin protein. Furthermore, recruitment of Skp1 to chromatin and ubiquitination of chromatin-bound β-catenin are abolished upon TRRAP knock-down, leading to an abnormal retention of β-catenin at the chromatin and concomitant hyperactivation of the canonical Wnt pathway. These results demonstrate that there is a distinct regulatory mechanism for β-catenin ubiquitination/destruction acting in the nucleus which functionally complements cytoplasmic destruction of β-catenin and prevents its oncogenic stabilization and chronic activation of the canonical Wnt pathway.