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

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 helicase-containing 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.

Automated summary

In Arabidopsis thaliana, the activity of the Bloom syndrome complex, which is crucial for maintaining genome integrity, is controlled by selective autophagy. The DNA damage regulator KNO1 facilitates autophagic degradation of RMI1, a structural component of the complex, leading to increased homologous recombination. Reduced autophagic activity makes plants hypersensitive to DNA damage. KNO1 itself is stabilized by the ubiquitin-proteasome system upon DNA damage, mediated by UBP12 and UBP13 deubiquitinases. These findings reveal a regulatory cascade of interconnected protein degradation steps that fine-tune the homologous recombination response to DNA damage.