Budding yeast Dpb4 (POLE3/CHRAC17 in mammals) is a highly conserved histone fold protein that is shared by two protein complexes: the chromatin remodeler ISW2/hCHRAC and the DNA polymerase ε (Pol ε) holoenzyme. In Saccharomyces cerevisiae, Dpb4 forms histone-like dimers with Dls1 in the ISW2 complex and with Dpb3 in the Pol ε complex. Here, we show that Dpb4 plays two functions in sensing and processing DNA double-strand breaks (DSBs). Dpb4 promotes histone removal and DSB resection by interacting with Dls1 to facilitate the association of the Isw2 ATPase to DSBs. Furthermore, it promotes checkpoint activation by interacting with Dpb3 to facilitate the association of the checkpoint protein Rad9 to DSBs. Persistence of both Isw2 and Rad9 at DSBs is enhanced by the A62S mutation that is located in the Dpb4 histone fold domain and increases Dpb4 association at DSBs. Thus, Dpb4 exerts two distinct functions at DSBs depending on its interactors.
Casari, E., Gobbini, E., Gnugnoli, M., Mangiagalli, M., Clerici, M., & Longhese, M. (2021). Dpb4 promotes resection of DNA double-strand breaks and checkpoint activation by acting in two different protein complexes. NATURE COMMUNICATIONS, 12(1), 4750-4764 [10.1038/s41467-021-25090-9].
Citazione: | Casari, E., Gobbini, E., Gnugnoli, M., Mangiagalli, M., Clerici, M., & Longhese, M. (2021). Dpb4 promotes resection of DNA double-strand breaks and checkpoint activation by acting in two different protein complexes. NATURE COMMUNICATIONS, 12(1), 4750-4764 [10.1038/s41467-021-25090-9]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | No | |
Titolo: | Dpb4 promotes resection of DNA double-strand breaks and checkpoint activation by acting in two different protein complexes | |
Autori: | Casari, E; Gobbini, E; Gnugnoli, M; Mangiagalli, M; Clerici, M; Longhese, M | |
Autori: | CASARI, ERIKA (Primo) GOBBINI, ELISA (Secondo) LONGHESE, MARIA PIA (Ultimo) (Corresponding) | |
Data di pubblicazione: | 2021 | |
Lingua: | English | |
Rivista: | NATURE COMMUNICATIONS | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/s41467-021-25090-9 | |
Appare nelle tipologie: | 01 - Articolo su rivista |
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