Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Genes (Basel). 2022 Jan 28;13(2):249. doi: 10.3390/genes13020249.
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 () must be the product of the stoichiometry of the MCM replicative helicase loaded at the origin () and the probability with which that MCM is activated (). This framework emphasizes that mechanistic understanding of replication timing must focus on MCM loading and activation and can be simplified to the equation = *.
复制定时的随机模型假设,原点点火时间受原点点火概率的调节,早期点火原点具有高点火概率,晚期点火原点具有较低的点火概率。然而,它们并没有深入探讨为什么一个原点的点火概率应该高于另一个原点。在这里,通过注意到点火概率()必须是在原点装载的 MCM 复制解旋酶的化学计量()与该 MCM 被激活的概率()的乘积,可以提出一个简单的框架来解决这个问题。这个框架强调了对复制定时的机制理解必须集中在 MCM 加载和激活上,可以简化为方程 = *。