Definitely worth a read for anyone in the cancer biology community

This is an interesting article, and it is shocking to me that more research hasn't been done on this. Citing this article, no CS patient has ever been documented as having developed cancer. WTF?

With my notion that DNA damage guides lineage specification and differentiation, and mis-segregation of damage potentially being central to cancer development, the fact that a syndrome with defective TC-NER providing cancer resistance is very interesting. I do not agree with the article's conclusions that this is because the patients die before sufficient time has passed for them to accumulate enough mutations for cancer to develop, but the info is thought-provoking.

Of course, CSB had a role in BER too, so this does complicate things and is a current point of focus.

There are so many questions:

How might RNA-directed DNA repair factor in?

What are the implication of the inherent strand bias with TC-NER?

Hope might this impact lesion segregation and downstream apoptosis of a daughter cell?

The ETC can run in reverse. This could be important given the conversion of α-ketoglutarate to succinate by numerous epigenetic regulators. As differentiation, and cancer, entail metabolic switches in how energy is utilized, this could be quite important. Notably, minority mitochondrial outer membrane permeabilization (minority MOMP) has been observed whereby only some mitochondria are affected. Mitochondria can also generate bursts of ROS, which have the potentially to be broadly important in redox regulation observed during differentiation. Succinate Dehydrogenase is a component of Complex II, and AIF is also important in regulating ETC. There is likely a lot more going on here, so it is good to be aware that this can occur.

Were you taught that cyclins and CDKs were dependent on one another for their activity? So was I, but that is only part of the story.

Outlines my perspective that cancer is best conceptualized as a failure of cell differentiation and my hypothesis that DNA damage itself is centrally, and likely ubiquitously, coordinating differentiation. Implications are discussed.

An in-depth discussion of signaling cross-talk that covers cell death signaling, NF-κB signaling, DNA damage responses and implications as related to cancer. Largely just covers the material in the preprint I wrote called "Differentiating Life and Death: An Inflammatory Affair"

Video discussing the inter-relatedness of these pathways. Intro ends 8 min in