The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition

It has been proposed that ATR kinase senses the completion of DNA replication to initiate the S/G2 transition. In contrast to this model, we show here that the TRESLIN-MTBP complex prevents a premature entry into G2 from early S-phase independently of ATR/CHK1 kinases. TRESLIN-MTBP acts transiently at pre-replication complexes (preRCs) to initiate origin firing and is released after the subsequent recruitment of CDC45. This dynamic behavior of TRESLIN-MTBP implements a monitoring system that checks the activation of replica-tion forks and senses the rate of origin firing to prevent the entry into G2. This system detects the decline in the number of origins of replication that naturally occurs in very late S, which is the signature that cells use to determine the completion of DNA replication and permit the S/G2 transition. Our work introduces TRESLIN-MTBP as a key player in cell-cycle control independent of canonical checkpoints.

Automated summary

In contrast to existing models, the TRESLIN-MTBP complex can prevent premature entry into G2 independently of ATR/CHK1 kinases in early S-phase. It acts as a monitoring system that checks the activation of replication forks and senses the rate of origin firing to prevent premature entry into G2.