RNF8 has both KU-dependent and independent roles in chromosomal break repair.
Nucleic Acids Res
; 48(11): 6032-6052, 2020 06 19.
Article
en En
| MEDLINE
| ID: mdl-32427332
ABSTRACT
Chromosomal double strand breaks (DSBs) can initiate several signaling events, such as ubiquitination, however the precise influence of such signaling on DSB repair outcomes remains poorly understood. With an RNA interference screen, we found that the E3 ubiquitin ligase RNF8 suppresses a deletion rearrangement mediated by canonical non-homologous end joining (C-NHEJ). We also found that RNF8 suppresses EJ without insertion/deletion mutations, which is a hallmark of C-NHEJ. Conversely, RNF8 promotes alternative EJ (ALT-EJ) events involving microhomology that is embedded from the edge of the DSB. These ALT-EJ events likely require limited end resection, whereas RNF8 is not required for single-strand annealing repair involving extensive end resection. Thus, RNF8 appears to specifically facilitate repair events requiring limited end resection, which we find is dependent on the DSB end protection factor KU. However, we also find that RNF8 is important for homology-directed repair (HDR) independently of KU, which appears linked to promoting PALB2 function. Finally, the influence of RNF8 on EJ is distinct from 53BP1 and the ALT-EJ factor, POLQ. We suggest that RNF8 mediates both ALT-EJ and HDR, but via distinct mechanisms, since only the former is dependent on KU.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Rotura Cromosómica
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Ubiquitina-Proteína Ligasas
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Proteínas de Unión al ADN
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Reparación del ADN por Unión de Extremidades
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Reparación del ADN por Recombinación
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Autoantígeno Ku
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos