Non-homologous end joining

The cell must repair that double-strand break, and it usually defaults to its fastest, most robust repair pathway, which is called non-homologous enjoining.

Or NHEJ.

But NHEJ is an incredibly sloppy process.

Sloppy how?

The cell essentially takes the two broken ends of the DNA and frantically glues them back together as quickly as possible.

It allows scientists to systematically turn off genes and petri dishes to figure out what they do.

But in a clinical setting.

For treating a living, breathing human patient, relying on the unpredictable, chaotic nature of NHEJ is incredibly dangerous.

So it's basically also self-protection for the DNA.

[laughs] NHEJ, non-homologous end joining.

And I mean, also there, uh, histone modifications play a role because H2A is then, so not H3 or H4 but H2A, if you have H2AV there and if you have, uh, like, modifications on H2A, then this will be sites that need to be repaired, that can be repaired, that need to be open because the repair mechanisms need to come in, right? Another area of epigenetic chromatin regulation.

Whew.

We've talked about DNA repair in the past.

Nucleotide excision repair, but also homologous recombination and non-homologous, because they're all linked, and joining, which is called NHEJ.

So homologous recombination, HR.

Non-homologous adjoining, NHEJ.

Those are different associated nucleotide excision repair complexes linked to DNA repair.

Now, what happens when you deplete SIRT1 in mouse fibroblasts, cell culture? It impairs the DNA damage response, and it leads to that all-encompassing Genomic instability.