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Nonhomologous end joining: new accessory factors fine tune the machinery.

Abstract
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.
AuthorsDipayan Ghosh, Sathees C Raghavan
JournalTrends in genetics : TIG (Trends Genet) Vol. 37 Issue 6 Pg. 582-599 (06 2021) ISSN: 0168-9525 [Print] England
PMID33785198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2021 Elsevier Ltd. All rights reserved.
Chemical References
  • DNA-Binding Proteins
  • IFFO1 protein, human
  • Intermediate Filament Proteins
  • PAXX protein, human
  • Proteins
  • TARDBP protein, human
  • Ribonucleases
  • DNA Helicases
  • ERCC6L2 protein, human
Topics
  • Animals
  • DNA End-Joining Repair (physiology)
  • DNA Helicases (genetics, metabolism)
  • DNA-Binding Proteins (genetics, metabolism)
  • Humans
  • Intermediate Filament Proteins (genetics, metabolism)
  • Proteins (genetics, metabolism)
  • Ribonucleases (genetics, metabolism)

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