The Ubiquitin-Proteasome System and DNA Repair

Falaschetti, Christine A.; Mirkin, Emily C; Raha, Sumita; Paunesku, Tatjana; Woloschak, Gayle E.

doi:10.5772/24431

Cited by 3 publications

(3 citation statements)

References 201 publications

(256 reference statements)

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“…KNO1 is at the crossroad of the two major protein degradation systems of the cell, the ubiquitin–proteasome system (UPS) and autophagy (Pohl & Dikic, 2019). While selective control of proteins amount via the proteasome pathway is frequently seen in animals and plants in diverse biological processes including the DNA damage response pathway (Moon et al , 2004; Falaschetti et al , 2011), we have only limited insight on how autophagy is linked to DNA repair. The emerging picture is based on studies in animals and yeast, while nothing has been described for plants.…”

Section: Discussionmentioning

confidence: 97%

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KNO1‐mediated autophagic degradation of the Bloom syndrome complex component RMI1 promotes homologous recombination

et al. 2023

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Homologous recombination (HR) is a key DNA damage repair pathway that is tightly adjusted to the state of a cell. A central regulator of homologous recombination is the conserved helicasecontaining Bloom syndrome complex, renowned for its crucial role in maintaining genome integrity. Here, we show that in Arabidopsis thaliana, Bloom complex activity is controlled by selective autophagy. We find that the recently identified DNA damage regulator KNO1 facilitates K63-linked ubiquitination of RMI1, a structural component of the complex, thereby triggering RMI1 autophagic degradation and resulting in increased homologous recombination. Conversely, reduced autophagic activity makes plants hypersensitive to DNA damage. KNO1 itself is also controlled at the level of proteolysis, in this case mediated by the ubiquitin-proteasome system, becoming stabilized upon DNA damage via two redundantly acting deubiquitinases, UBP12 and UBP13. These findings uncover a regulatory cascade of selective and interconnected protein degradation steps resulting in a fine-tuned HR response upon DNA damage.

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Section: Discussionmentioning

confidence: 97%

“…autophagy (Pohl & Dikic, 2019). While selective control of proteins amount via the proteasome pathway is frequently seen in animals and plants in diverse biological processes including the DNA damage response pathway (Moon et al, 2004;Falaschetti et al, 2011),…”

mentioning

confidence: 99%

KNO1‐mediated autophagic degradation of the Bloom syndrome complex component RMI1 promotes homologous recombination

et al. 2023

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“…This discovery was honored by the Nobel Prize for chemistry in 2004. The ubiquitin-proteasome system is implicated through protein homeostasis in practically all aspects of cellular processes including DNA repair [11][12]. A nice example of DNA repair regulation through ubiquitination by UBR3 E3 ligase and subsequent protein degradation is the control of APE1 (Ref-1), a protein involved in DNA repair (mostly excision repair of abasic sites) and regulation of transcription [13].…”

Section: Ubiquitin As a Ptmmentioning

confidence: 99%