The C-terminus of Nej1 is critical for nuclear localization and non-homologous end-joining.

DNA Repair (Amst)

Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1. Electronic address:

Published: February 2014

Nej1 is an essential factor in the non-homologous end-joining (NHEJ) pathway and interacts with the DNA ligase complex, Lif1-Dnl4, through interactions with Lif1. We have mapped K331-V338 in the C-terminal region of Nej1 to be critical for its functionality during repair. Truncation and alanine scanning mutagenesis have been used to identify a motif in Nej1, KKRK (331-334), which is important for both nuclear targeting and NHEJ repair after localization. We have identified F335-V338 to be important for proper interaction with Lif1, however this region is not required for Nej1 recruitment to HO endonuclease-induced DNA double-strand breaks in vivo. Phenylalanine at position 335 is particularly important for the role of Nej1 in repair and the loss of association between Nej1 and Lif1 correlates with a decrease in cell survival upon either transient or continuous HO expression in nej1 mutants.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122420PMC
http://dx.doi.org/10.1016/j.dnarep.2013.12.002DOI Listing

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