f = m * a : A Framework for Investigating the Regulation of Replication Timing.

Stochastic models of replication timing posit that origin firing timing is regulated by origin firing probability, with early-firing origins having a high probability of firing and late-firing origins having a lower probability. However, they offer no insight into why one origin should have a higher firing probability than another. Here, a simple framework is suggested for how to approach the question by noting that the firing probability ( f ) must be the product of the stoichiometry of the MCM replicative helicase loaded at the origin ( m ) and the probability with which that MCM is activated ( a ). This framework emphasizes that mechanistic understanding of replication timing must focus on MCM loading and activation and can be simplified to the equation f = m * a .