RT Journal Article
T1 The Ubiquitin E3/E4 Ligase UBE4A Adjusts Protein Ubiquitylation and Accumulation at Sites of DNA Damage, Facilitating Double-Strand Break Repair.
A1 Baranes-Bachar, Keren
A1 Levy-Barda, Adva
A1 Oehler, Judith
A1 Reid, Dylan A
A1 Soria-Bretones, Isabel
A1 Voss, Ty C
A1 Chung, Dudley
A1 Park, Yoon
A1 Liu, Chao
A1 Yoon, Jong-Bok
A1 Li, Wei
A1 Dellaire, Graham
A1 Misteli, Tom
A1 Huertas, Pablo
A1 Rothenberg, Eli
A1 Ramadan, Kristijan
A1 Ziv, Yael
A1 Shiloh, Yosef
K1 DNA damage
K1 UBE4A
K1 double-strand breaks
K1 genome stability
K1 ubiquitin
AB Double-strand breaks (DSBs) are critical DNA lesions that robustly activate the elaborate DNA damage response (DDR) network. We identified a critical player in DDR fine-tuning: the E3/E4 ubiquitin ligase UBE4A. UBE4A's recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites. This pathway is essential for optimal end resection at DSBs, and its abrogation leads to upregulation of the highly mutagenic alternative end-joining repair at the expense of error-free homologous recombination repair. Our data uncover a critical regulatory level in the DSB response and underscore the importance of fine-tuning the complex DDR network for accurate and balanced execution of DSB repair.
YR 2018
FD 2018
LK http://hdl.handle.net/10668/12204
UL http://hdl.handle.net/10668/12204
LA en
DS RISalud
RD Apr 13, 2025