…as well as using experimental estimates of repair activity. Their analyses further indicate that SBS5 is not only the result of translesion synthesis, a mechanism of damage tolerance, but also of DNA repair, suggesting SBS5 results from the occasional recruitment of the same polymerase. 12/n

On that basis, they predicted that the number of mutations assigned to SBS5 should increase with multiple types of damage and relate to repair rates along the genome in predictable ways. These model predictions are met in data from tumors, somatic and germline datasets... 11/n

What Natanael & Marc realized is that such collateral mutagenesis leads multiple types of damage to be funneled into a single signature, which primarily reflects the error profile of a polymerase, rather than the damage sources. They conjectured that SBS5 reflects such a funnel. 10/n

Intriguingly, the number of mutations assigned to SBS5 increases linearly with time, in dividing cells as well as quiescent or post-mitotic ones (Alexandrov et al. 2015 Nature; Lodato et al. 2018 Science, Spisak et al. 2024 PLoS Biology). 5/n

These efforts have led to the identification of a number of mutagens and repair deficiencies. But a ubiquitous signature of single base substitutions identified by this approach, SBS5, has remained a mystery. 3/n

On that basis, they predicted that the number of mutations assigned to SBS5 should increase with multiple types of damage and relate to repair rates along the genome in predictable ways. These model predictions are met in data from tumors, somatic and germline datasets... 11/n

What Natanael & Marc realized is that such collateral mutagenesis leads multiple types of damage to be funneled into a single signature, which primarily reflects the error profile of a polymerase, rather than the damage sources. They conjectured that SBS5 reflects such a funnel. 10/n

Intriguingly, the number of mutations assigned to SBS5 increases with time, in dividing cells as well as quiescent or post-mitotic ones (Alexandrov et al. 2015 Nature; Lodato et al. 2018 Science, Spisak et al. 2024 PLoS Biology). 5/n

These efforts have led to the identification of a number of mutagens and repair deficiencies. But a ubiquitous signature of single base substitutions identified by this approach, SBS5, has remained a mystery. 3/n

Stream or attend a conference on Frontiers in Human Genetics at Columbia University (Oct 10 & 11), by registering here: events.columbia.edu/cal/event/ev...

For those in the NY area and beyond: a two day symposium on Frontiers In Human Genetics, October 10 & 11 2024. Registration is free but required.

Statement from AAUP of Barnard & Columbia about arrests on campus

For those in the NY area, SAVE THE DATE (& register) for a Symposium on Human Genetics at Columbia University: Oct 10-11 2024. Talks will also be streamed.

Congratulations to @choge.bsky.social, Dr. Carla Hoge!