Naslov
The protease SPRTN and SUMOylation coordinate DNA-protein crosslink repair to prevent genome instability

Autori
Ruggiano, Annamaria ; Vaz, Bruno ; Kilgas, Susan ; Popović, Marta ; Rodriguez-Berriguete, Gonzalo ; Singh, Abhay N. ; Higgins, Geoff S. ; Kiltie, Anne E. ; Ramadan, Kristijan

Izvornik
Cell Reports (2211-1247) 37 (2021), 10; 110080, 14

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
BRCA deficiency ; DNA-protein crosslink repair ; DNA replication ; genome stability ; formaldehyde toxicity ; homologous recombination ; synthetic lethality ; SPRTN protease ; SUMO ; ubiquitin

Sažetak
DNA-protein crosslinks (DPCs) are a specific type of DNA lesion in which proteins are covalently attached to DNA. Unrepaired DPCs lead to genomic instability, cancer, neurodegeneration, and accelerated aging. DPC proteolysis was recently identified as a specialized pathway for DPC repair. The DNA-dependent protease SPRTN and the 26S proteasome emerged as two independent proteolytic systems. DPCs are also repaired by homologous recombination (HR), a canonical DNA repair pathway. While studying the cellular response to DPC formation, we identify ubiquitylation and SUMOylation as two major signaling events in DNA replicationcoupled DPC repair. DPC ubiquitylation recruits SPRTN to repair sites, promoting DPC removal. DPC SUMOylation prevents DNA double-strand break formation, HR activation, and potentially deleterious genomic rearrangements. In this way, SUMOylation channels DPC repair toward SPRTN proteolysis, which is a safer pathway choice for DPC repair and prevention of genomic instability.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti, Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA