Highlighted Paper: The genome maintenance factor Mgs1 is targeted to sites of replication stress by ubiquitylated PCNA

Saugar I, Parker JL, Zhao S, Ulrich HD. The genome maintenance factor Mgs1 is targeted to sites of replication stress by ubiquitylated PCNA. Nucleic Acids Res. 2011 Sep 12. (Abstract) (Helle Ulrich)

Damage to a cell’s genetic material, the DNA, can result in cancer or ageing, and all organisms have therefore developed strategies to protect themselves from the harmful consequences of DNA damage. One of the cellular factors that contribute to genome protection, called WRNIP1 in human cells, is highly conserved among different organisms. In budding yeast, a simple fungus that is often used for studying the mechanisms of genome maintenance, the corresponding factor is called Mgs1. Whereas lack of this protein results in premature ageing and genetic instability, an excess of Mgs1 is equally dangerous to genome stability. However, the mechanism by which Mgs1 or human WRNIP1 protect DNA from damage is not well understood.

We have now discovered an important aspect of Mgs1 that determines how the protein is brought to its sites of action on damaged DNA. Both Mgs1 and WRNIP1 contain a conserved motif that recognises ubiquitin, a small protein that is used as a tag on other cellular factors to modulate their properties. At sites where DNA damage has caused problems with the duplication of the DNA, ubiquitin is attached to an essential replication factor called PCNA. Mgs1 then recognises the presence of the ubiquitin tag on PCNA as a signal to assemble at these regions. Our results suggest that Mgs1 might block the activity of an enzyme involved in the duplication of DNA, which would explain why the correct amount of Mgs1 is critical for its proper function. Our work has thus revealed how the activity of Mgs1 is controlled and directed towards the appropriate situation, and we expect that it will help us to better understand the role of the human protein WRNIP1 as well.