Created at 1:27 a.m. Jun, 28, 2025
Author: crunch_bono
Related Note: 1516938209170 1
Rationale for change

In nonhomologous end joining (NHEJ), dsDNA breaks are recognized by the Ku70/Ku80 heterodimer (Ku complex). The Ku heterodimer rapidly binds to DNA ends and serves as the primary sensor of DNA double-strand breaks. This binding recruits the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), forming the DNA-PK holoenzyme complex at the DNA break site. DNA-PKcs is essential for tethering DNA ends and orchestrating the assembly of downstream NHEJ factors. Following DNA-PKcs recruitment, the complex facilitates the recruitment and activation of Artemis, a nuclease that processes DNA ends to make them compatible for ligation. Artemis is activated by phosphorylation through DNA-PKcs, enabling it to trim overhangs or hairpins as needed. Additional end-processing enzymes, such as polynucleotide kinase/phosphatase (PNKP) and DNA polymerases μ and λ, may also participate depending on the nature of the DNA ends. Once the DNA ends are properly processed, the XRCC4–DNA ligase IV complex, often in association with XLF (Cernunnos) and PAXX, mediates the final ligation step to restore DNA integrity. [1-5]

The MRN complex (MRE11-RAD50-NBS1) is not a canonical component of the NHEJ pathway. Instead, MRN is primarily involved in homologous recombination and alternative end-joining pathways, where it facilitates DNA end resection, especially in S and G2 phases of the cell cycle. [1-5]

All this information is also found in the photo in the extra section. The main text has incorrect information. References:


1. Nonhomologous DNA End-Joining for Repair of DNA Double-Strand Breaks.
Pannunzio NR, Watanabe G, Lieber MR.
The Journal of Biological Chemistry. 2018;293(27):10512-10523. doi:10.1074/jbc.TM117.000374.
2. Different DNA End Configurations Dictate Which NHEJ Components Are Most Important for Joining Efficiency.
Chang HHY, Watanabe G, Gerodimos CA, et al.
The Journal of Biological Chemistry. 2016;291(47):24377-24389. doi:10.1074/jbc.M116.752329.
3. Structural Insights Into NHEJ: Building Up an Integrated Picture of the Dynamic DSB Repair Super Complex, One Component and Interaction at a Time.
Williams GJ, Hammel M, Radhakrishnan SK, et al.
DNA Repair. 2014;17:110-20. doi:10.1016/j.dnarep.2014.02.009.
4. Repair of Ionizing Radiation-Induced DNA Double-Strand Breaks by Non-Homologous End-Joining.
Mahaney BL, Meek K, Lees-Miller SP.
The Biochemical Journal. 2009;417(3):639-50. doi:10.1042/BJ20080413.
5. Multicomponent Assemblies in DNA-double-strand Break Repair by NHEJ.
Hnízda A, Blundell TL.
Current Opinion in Structural Biology. 2019;55:154-160. doi:10.1016/j.sbi.2019.03.026.

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