Treslin (also known as TICRR; orthologue of yeast Sld3) is an essential replication protein regulated by cyclin-dependent kinases and DNA damage. Diffley and colleagues identify Mdm two binding protein (MTBP) as a crucial Treslin partner at replication origins (Science 340, 981–984; 2013)

Using mass spectrometry, the authors identified MTBP as a Treslin binding partner. The authors confirmed the existence of a ternary complex that also contains the known Treslin-binding partner TopBP1 in cells. A Treslin mutant unable to interact with MTBP is unable to rescue DNA replication in Treslin-depleted cells. Time-lapse microscopy of cells expressing a GFP-tagged version of replication marker PCNA revealed that S phase is slowed down in MTBP-depleted cells. DNA fibre analysis showed that this is because of reduced origin firing rather than reduced replication fork speed. Origin licensing protein Mcm2 was efficiently recruited to chromatin in MTPB-depleted cells, but levels of PCNA and components of the CMG helicase, a complex involved in DNA unwinding at replication forks, were reduced.

These findings reveal a role for the Treslin–MTBP–TopBP1complex in origin firing. MTBP is amplified in some cancers, and it will be interesting to investigate whether its role in replication is relevant in this context.