DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.

CDC7 kinase is crucial for DNA replication initiation and is involved in fork processing and replication stress response. Human CDC7 requires the binding of either DBF4 or DRF1 for its activity. However, it is unclear whether the two regulatory subunits target CDC7 to a specific set of substrates, thus having different biological functions, or if they act redundantly.

CDC7 inhibition drives an inflammatory response and a p53-dependent senescent-like state in breast epithelial cells.

Drugs that block DNA replication prevent cell proliferation, which may result in anticancer activity. The latter is dependent on the drug's mode of action as well as on cell type-dependent responses to treatment. The inhibition of Cell division cycle 7-related protein kinase (CDC7), a key regulator of DNA replication, decreases the efficiency of origin firing and hampers the restarting of paused replication forks.

Discovery and characterization of noncanonical E2-conjugating enzymes.

E2-conjugating enzymes (E2s) play a central role in the enzymatic cascade that leads to the attachment of ubiquitin to a substrate. This process, termed ubiquitylation, is required to maintain cellular homeostasis and affects almost all cellular process. By interacting with multiple E3 ligases, E2s dictate the ubiquitylation landscape within the cell.

CDC7 kinase promotes MRE11 fork processing, modulating fork speed and chromosomal breakage.

The CDC7 kinase is essential for the activation of DNA replication origins and has been implicated in the replication stress response. Using a highly specific chemical inhibitor and a chemical genetic approach, we now show that CDC7 activity is required to coordinate multiple MRE11-dependent processes occurring at replication forks, independently from its role in origin firing. CDC7 localizes at replication forks and, similarly to MRE11, mediates active slowing of fork progression upon mild topoisomerase inhibition.