VIRTUAL Molecular Biology and Biophysics Journal Club
Presenter: Gianluca Arianna
Paper Title: “Molecular basis for assembly of the shieldin complex and its implications for NHEJ”
Author & Journal Info: Liang, L., Feng, J., Zuo, P., Yang, J., Lu, Y., & Yin, Y. (2020). Molecular basis for assembly of the shieldin complex and its implications for NHEJ. Nature Communications, 11(1972), 1-15. doi: 10.1038/s41467-020-15879-5
Paper link: https://www.nature.com/articles/s41467-020-15879-5#Sec30
Supplementary Info Link:https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-020-15879-5/MediaObjects/41467_2020_15879_MOESM1_ESM.pdf
Brief Description: Rev7 (MAD2B/MAD2L2) is a multi-functional hub protein involved in the regulation and coordination of several DNA damage response and cell cycle pathways. This paper elucidates the structural determinants of Rev7’s interaction within the Shieldin complex (SHLD1/SHLD2/SHLD3/Rev7), which coordinates with 53BP1-RIF1 to promote non-homologous end joining (NHEJ) following a double stranded break (DSB) in DNA. In particular, this work examines the solved crystal structure of a SHLD3-Rev7-SHLD2 ternary complex which shows Rev7 in a closed-open conformational dimer (C-Rev7-O-Rev7). Excitingly, this represents the first structural characterization of the open conformation of Rev7, which thus far has proven difficult to isolate for study. The authors demonstrate that the Rev7 binding motif (RBM) of SHLD3 is crucial for the formation of the C-Rev7-O-Rev7 dimer, which is further stabilized by SHLD2. Importantly, they determine that the stabilization of O-Rev7 within the Shieldin complex is important for proper NHEJ function. They also show that the structure of this complex influences the Rev7 interaction with Rev1 and Rev3, thereby serving as a regulatory bridge between NHEJ and the DNA damage tolerance pathway, translesion synthesis (TLS).
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