S Phase Duration Is Determined by Local Rate and Global Organization of Replication

Avraham Greenberg, Itamar Simon*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


The duration of the cell cycle has been extensively studied and a wide degree of variability exists between cells, tissues and organisms. However, the duration of S phase has often been neglected, due to the false assumption that S phase duration is relatively constant. In this paper, we describe the methodologies to measure S phase duration, summarize the existing knowledge about its variability and discuss the key factors that control it. The local rate of replication (LRR), which is a combination of fork rate (FR) and inter-origin distance (IOD), has a limited influence on S phase duration, partially due to the compensation between FR and IOD. On the other hand, the organization of the replication program, specifically the amount of replication domains that fire simultaneously and the degree of overlap between the firing of distinct replication timing domains, is the main determinant of S phase duration. We use these principles to explain the variation in S phase length in different tissues and conditions.

Original languageAmerican English
Article number718
Issue number5
StatePublished - 7 May 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • DNA replication
  • S phase
  • cell cycle
  • fork rate
  • inter-origin distance
  • replication timing


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