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01814nam a2200229Ia 4500 |
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10.1016-j.dnarep.2022.103332 |
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220706s2022 CNT 000 0 und d |
| 020 |
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|a 15687864 (ISSN)
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| 245 |
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|a Multifunctional properties of Nej1XLF C-terminus promote end-joining and impact DNA double-strand break repair pathway choice
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|b Elsevier B.V.
|c 2022
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|z View Fulltext in Publisher
|u https://doi.org/10.1016/j.dnarep.2022.103332
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|a A DNA double strand break (DSB) is primarily repaired by one of two canonical pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ requires no or minimal end processing for ligation, whereas HR requires 5’ end resection followed by a search for homology. The main event that determines the mode of repair is the initiation of 5’ resection because if resection starts, then NHEJ cannot occur. Nej1 is a canonical NHEJ factor that functions at the cross-roads of repair pathway choice and prior to its function in stimulating Dnl4 ligase. Nej1 competes with Dna2, inhibiting its recruitment to DSBs and thereby inhibiting resection. The highly conserved C-terminal region (CTR) of Nej1 (330−338) is important for two events that drive NHEJ as it stimulates ligation and inhibits resection, but it is dispensable for end-bridging. By combining nej1 point mutants with nuclease-dead dna2-1, we find that Nej1-F335 is essential for end-joining whereas V338 promotes NHEJ indirectly by inhibiting Dna2-mediated resection. © 2022
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|a 5' resection
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|a Dna2
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|a DSB repair
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|a Nej1
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|a Non-homologous end-joining (NHEJ)
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|a Repair pathway choice
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|a Adam, N.
|e author
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|a Cobb, J.A.
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|a Mojumdar, A.
|e author
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| 773 |
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|t DNA Repair
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