The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity. (https://pubmed.ncbi.nlm.nih.gov/38554706/)

These scientists were studying how cells copy their DNA, which is important for making sure our bodies work properly. They found that a special group of proteins called the CMG helicase needs to be unfolded by another protein called VCP/p97 in order to stop the DNA copying process. They also discovered that other proteins involved in DNA copying are not unfolded in the same way, which means there are different ways these proteins are controlled in the cell.

To learn more about how these proteins work together, the scientists identified a new group of proteins called SPATA5-SPATA5L1 along with their partners C1orf109-CINP (55LCC). They used a special technique called structural biology to see how these proteins interact with each other. They found that the SPATA5-SPATA5L1 proteins form a funnel-like shape above an ATPase motor, which is like a tiny machine that helps the proteins do their job.

When they studied cells that were missing the 55LCC complex, they found that the cells had problems with DNA copying, which caused stress and instability in the chromosomes. The 55LCC complex was also found to have a special activity that helps it work better when DNA is being copied. This activity helps to cut other proteins involved in DNA copying when there is damage to the DNA.

Overall, these findings show that the 55LCC complex is very important for making sure DNA copying happens correctly and that our cells stay healthy. This study also gives us clues about why some people may have certain genetic disorders related to these proteins.

Krishnamoorthy V., Foglizzo M., Dilley RL., Wu A., Datta A., Dutta P., Campbell LJ., Degtjarik O., Musgrove LJ., Calabrese AN., Zeqiraj E., Greenberg RA. The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity. Cell. 2024 Apr 25;187(9):2250-2268.e31. doi: 10.1016/j.cell.2024.03.002. Epub 2024 Mar 29.