Obi1-KO Mouse

Obi1, also known as C13ORF7/RNF219, is associated with the ORC complex. It functions as an ORC ubiquitin ligase, promoting DNA replication origin firing [1]. This process is crucial in the cell cycle as it allows for the proper initiation of DNA replication, which is essential for cell division and the maintenance of genomic integrity.

In human cells, OBI1 silencing leads to defective origin firing, shown by reduced CMG-complex formation, without impacting pre-replicative complex (pre-RC) establishment [1]. OBI1 catalyzes the multi-mono-ubiquitylation of chromatin-bound ORC3 and ORC5 during S-phase, and expression of non-ubiquitylable ORC3/5 mutants impairs origin firing, demonstrating their importance as OBI1 substrates for this process [1].

In summary, OBI1 plays a vital role in DNA replication origin activation through its ubiquitin ligase activity on ORC3 and ORC5. Understanding the function of OBI1, especially through such loss-of-function studies in human cells, is crucial for elucidating the mechanisms of DNA replication and potentially for understanding related diseases where DNA replication goes awry.

References:

1. Coulombe, Philippe, Nassar, Joelle, Peiffer, Isabelle, Bocquet, Stéphane, Méchali, Marcel. 2019. The ORC ubiquitin ligase OBI1 promotes DNA replication origin firing. In Nature communications, 10, 2426. doi:10.1038/s41467-019-10321-x. https://pubmed.ncbi.nlm.nih.gov/31160578/