Non Homologous end joining

Non Homologous end joining (NHEJ) is one of the most effective major pathways of double stranded break repair mechanism.

The reason behind the double-strand break:

Ionizing radiation, oxidizing agents and replication errors may cause double-strand break in DNA. If these lesions were left unrepaired, they would lead to the breakdown of chromosomes into smaller fragments.

The efficient error-prone pathway:

NHEJ is a process by which the cell can repair strand breaks without the need for a homologous template. NHEJ often leads to insertions or deletions of nucleotides (termed indels) at the site of repair. Hence, NHEJ is highly efficient but error-prone pathway.

Occurrence:

Non homologous end joining is present throughout the cell cycle but is particularly common in the G0 and G1 phases whereas HDR (Homology-directed repair) predominates in the S and G2 phases, when a homology sister chromatid is available as a template for repair.

The mechanism of Non Homologous End joining:

1. NHEJ is considered as an emergency solution to the repair of double-strand break.
2. In this process, broken ends are juxtaposed and rejoined by DNA ligation, generally with the loss of one or more nucleotides at the site of joining.
3. The first stage in this process is the recognition of the broken ends by a heterodimer Ku70 and Ku80.
4. Ku proteins allow DNA-dependent protein kinase (DNA-PKcs) to act.
5. Phosphorylation by this kinase triggers the recruitment of end processing factors, including the nuclease Artemis, that trim the DNA ends.
6. This makes the the DNA compatible for ligation.
7. Artemis shows both endo and exonuclease activities and trims the DNA ends.
8. The final joining of double-strand ends is carried out by the DNA ligase IV in association with XRCC4.

The schematic representation of non homologous end joining:

Other related notes:

1. Base excision repair: https://thebiologyislove.com/base-excision-repair/
2. Nucleotide excision repair: https://thebiologyislove.com/nucleotide-excision-repair/

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