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    Nonhomologous DNA end joining (NHEJ) is one of the major DNA double-strand break (DSB) repair pathways in eukaryotes. The well-known critical proteins involved in NHEJ include Ku70/80, DNA-PKcs, Artemis, DNA pol λ/μ, DNA ligase IV-XRCC4, and XLF. Recent studies have added a number of new proteins to the NHEJ repertoire namely paralog of XRCC4 and XLF (PAXX), modulator of retroviral infection (MRI)/ cell cycle regulator of NHEJ (CYREN), transactivation response DNA-binding protein (TARDBP) of 43 kDa (TDP-43), intermediate filament family orphan (IFFO1), ERCC excision repair 6 like 2 (ERCC6L2), and RNase H2. PAXX acts as a stabilizing factor for the main NHEJ components. MRI/CYREN seems to play a dual role stimulating NHEJ in the G1 phase of the cell cycle, while inhibiting the pathway in the S and G2 phases. TDP-43 can recruit the ligase IV-XRCC4 complex to the DSB sites and stimulate ligation in neuronal cells. RNase H2 excises out the ribonucleotides inserted during repair by DNA polymerase μ/TdT. This review provides a brief glimpse into how these new partners were discovered and their contribution to the mechanism and regulation of NHEJ. Copyright © 2021 Elsevier Ltd. All rights reserved.


    Dipayan Ghosh, Sathees C Raghavan. Nonhomologous end joining: new accessory factors fine tune the machinery. Trends in genetics : TIG. 2021 Jun;37(6):582-599

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    PMID: 33785198

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