DDI1

Last update 08 May 2025

Basic Info

Synonyms

DDI1, DNA damage inducible 1 homolog 1, FLJ36017

+ [1]

Introduction

Probable aspartic protease (Probable). Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2 (Probable). Required, with DDI2, for cellular survival following replication stress. Together or redudantly with DDI2, removes RTF2 from stalled forks to allow cell cycle progression after replication stress and maintains genome integrity (PubMed:29290612).

100 Clinical Results associated with DDI1

100 Translational Medicine associated with DDI1

0 Patents (Medical) associated with DDI1

Literatures (Medical) associated with DDI1

05 Mar 2024·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

Proteasome condensate formation is driven by multivalent interactions with shuttle factors and ubiquitin chains

Q1 · CROSS-FIELD

Article

Author: Vontz, Gabrielle ; Lee, Stella Y. ; Waite, Kenrick A. ; Roelofs, Jeroen

03 Jul 2023·The EMBO Journal

Ubx5‐Cdc48 assists the protease Wss1 at DNA‐protein crosslink sites in yeast

Article

Author: Serbyn, Nataliia ; Noireterre, Audrey ; Stutz, Françoise ; Bagdiul, Ivona

AbstractDNA‐protein crosslinks (DPCs) pose a serious threat to genome stability. The yeast proteases Wss1, 26S proteasome, and Ddi1 are safeguards of genome integrity by acting on a plethora of DNA‐bound proteins in different cellular contexts. The AAA ATPase Cdc48/p97 is known to assist Wss1/SPRTN in clearing DNA‐bound complexes; however, its contribution to DPC proteolysis remains unclear. Here, we show that the Cdc48 adaptor Ubx5 is detrimental in yeast mutants defective in DPC processing. Using an inducible site‐specific crosslink, we show that Ubx5 accumulates at persistent DPC lesions in the absence of Wss1, which prevents their efficient removal from the DNA. Abolishing Cdc48 binding or complete loss of Ubx5 suppresses sensitivity of wss1∆ cells to DPC‐inducing agents by favoring alternate repair pathways. We provide evidence for cooperation of Ubx5‐Cdc48 and Wss1 in the genotoxin‐induced degradation of RNA polymerase II (RNAPII), a described candidate substrate of Wss1. We propose that Ubx5‐Cdc48 assists Wss1 for proteolysis of a subset of DNA‐bound proteins. Together, our findings reveal a central role for Ubx5 in DPC clearance and repair.

26 Jun 2023·bioRxiv : the preprint server for biology

Proteasome condensate formation is driven by multivalent interactions with shuttle factors and K48-linked ubiquitin chains.

Author: Lee, Stella Y ; Roelofs, Jeroen ; Vontz, Gabrielle ; Waite, Kenrick A

Stress conditions can cause the relocalization of proteasomes to condensates in yeast and mammalian cells. The interactions that facilitate the formation of proteasome condensates, however, are unclear. Here, we show that the formation of proteasome condensates in yeast depends on long K48-linked ubiquitin chains together with the proteasome shuttle factors Rad23 and Dsk2. These shuttle factors colocalize to these condensates. Strains deleted for the third shuttle factor gene, DDI1 , show proteasome condensates in the absence of cellular stress, consistent with the accumulation of substrates with long K48-linked ubiquitin chains that accumulate in this mutant. We propose a model where the long K48-linked ubiquitin chains function as a scaffold for the ubiquitin binding domains of the shuttle factors and the proteasome, allowing for the multivalent interactions that further drive condensate formation. Indeed, we determined different intrinsic ubiquitin receptors of the proteasome (Rpn1, Rpn10, and Rpn13) are critical under different condensate inducing conditions. In all, our data support a model where the cellular accumulation of substrates with long ubiquitin chains, potentially due to reduced cellular energy, allows for proteasome condensate formation. This suggests that proteasome condensates are not simply for proteasome storage, but function to sequester soluble ubiquitinated substrates together with inactive proteasomes.SignificanceStress conditions can cause the relocalization of proteasomes to condensates in yeast as well as mammalian cells. Our work shows that the formation of proteasome condensates in yeast depends on long K48-linked ubiquitin chains, the proteasome binding shuttle factors Rad23 and Dsk2 and proteasome intrinsic ubiquitin receptors. Here, different receptors are critical for different condensate inducers. These results indicate distinct condensates can form with specific functionality. Our identification of key factors involved in the process is crucial for understanding the function of proteasome relocalization to condensates. We propose that cellular accumulation of substrates with long ubiquitin chains results in the formation of condensates comprising those ubiquitinated substrates, proteasomes, and proteasome shuttle factors, where the ubiquitin chains serve as the scaffold for condensate formation.

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DDI1

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