Stefan Jentsch

..We demonstrate that these modifications differentially affect resistance to DNA damage, and that damage-induced PCNA ubiquitination is elementary for DNA repair and occurs at the same conserved residue in yeast and humans...

..We discuss how Cdc48 might use this 'gearbox activity' to control protein fate and propose a similar mode of action for the 19S cap of the proteasome...

..In this chapter we will illustrate some key functions of ubiquitin and SUMO in the control of selected DNA repair pathways...

..Our finding suggests a model in which SUMO-modified PCNA recruits Srs2 in S phase in order to prevent unwanted recombination events of replicating chromosomes...

..We propose that the balance between the distinct substrate-processing cofactors may determine whether a substrate is multiubiquitylated and routed to the proteasome for degradation or deubiquitylated and/or released for other purposes...

..We therefore propose that the RAD6 pathway acts on single-stranded gaps left behind newly restarted replication forks...

..Our study thus indicates that PCNA, a central matchmaker for replication-linked functions, is also crucially involved in the establishment of cohesion in S phase...

..In yeast, this escort pathway guides a transcription factor from its activation in the cytosol to its final degradation and also mediates proteolysis at the endoplasmic reticulum by the ERAD pathway...

..Furthermore, our data indicate that sumoylation becomes particularly relevant for those Rad52 molecules that are engaged in recombination...

..Thus, our findings identify Sly1 as a discriminating regulator of SNARE levels and indicate that Sly1-controlled ERAD might regulate the balance between different Qa-SNARE proteins...

..Switching of PCNA partners may be triggered by affinity-driven competition, phosphorylation, proteolysis, and modification of PCNA by ubiquitin and SUMO...

..This suggests that the Pin1 activity is often translated into a fate-determining ubiquitylation switch, and that Pin1 may affect the degree of substrate ubiquitylation in other pathways as well...

..Our study indicates a novel mechanism for splice site utilization that is guided by non-covalent modification of the spliceosome by an unconventional ubiquitin-like modifier...

..Furthermore, we provide evidence that the ability of the proteasome to initiate proteolysis from an internal site and to proceed via bidirectional polypeptide degradation may be relevant for the complete degradation of proteins as well...

..Thus, Red1, in addition to its structural role in the SC, is a crucial coordinator of meiosis by coupling checkpoint signaling to SC formation...

..How distinct protein domains are spared from degradation remains a matter of debate. Here, we discuss several models and suggest a novel mechanism for proteasomal processing...

..Here we discuss procedures that can circumvent identification problems and describe methods for their verification...

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..Thus, a persistent DSB induces a multifaceted response, which is linked to a specific chromatin mark...

..Thus our findings suggest that autophagy has a broader role than previously assumed, and that cell renovation by clearing from superfluous large macromolecular assemblies, such as MRs, is an important autophagic function...

..We propose that BRUCE coordinates multiple steps required for abscission and that ubiquitylation may be a crucial trigger...

..Thus, although BRUCE is broadly expressed in embryonic, extraembryonic, and adult mouse tissues, this bifunctional protein might play a unique role in normal trophoblast differentiation and embryonic survival...

..Examples are proteins of the mammalian NF-kappaB family and the yeast proteins SPT23 and MGA2. In this review, we summarize the available data and suggest a mechanistic model for proteasomal processing...

..Our work suggests that, owing to its two activities and its localization, BRUCE may function as a specialized regulator of cell death pathways...

..We propose that HUB1 may act as a novel protein modulator through the formation of tight, possibly noncovalent interactions with target proteins...

..We propose that CDC48(UFD1/NPL4) functions as a segregase that liberates ubiquitylated proteins from non-modified partners...

..Moreover, key regulators of apoptosis themselves seem to have an active part in the proteolytic inactivation of death executors...

..This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases...

..Our study also suggests a key role of sumoylation for nucleolar dynamics, perhaps in the compartmentalization of nuclear activities...