Behavior of replication origins in Eukaryota - spatio-temporal dynamics of licensing and firing

Cell Cycle. 2015;14(14):2251-64. doi: 10.1080/15384101.2015.1056421. Epub 2015 Jun 1.


Although every organism shares some common features of replication, this process varies greatly among eukaryotic species. Current data show that mathematical models of the organization of origins based on possibility theory may be applied (and remain accurate) in every model organism i.e. from yeast to humans. The major differences lie within the dynamics of origin firing and the regulation mechanisms that have evolved to meet new challenges throughout the evolution of the organism. This article elaborates on the relations between chromatin structure, organization of origins, their firing times and the impact that these features can have on genome stability, showing both differences and parallels inside the eukaryotic domain.

Keywords: APC, anaphase promoting complex; ARS, autonomously replicating sequences; ATR, ataxia telangiectasia mutated and Rad3-related kinase; C-Frag, chromosome fragmentation; CDK, cyclin-dependent kinase; CDT, C-terminus domain; CEN, centromere; CFSs, chromosome fragile sites; CIN, chromosome instability; CMG, Cdc45-MCM-GINS complex; Cdc45, cell division control protein 45; Cdc6, cell division control protein 6; Cdt1, chromatin licensing and DNA replication factor 1; Chk1, checkpoint kinase 1; Clb2, G2/mitotic-specific cyclin Clb2; DCR, Ddb1-Cu14a-Roc1 complex; DDK, Dbf-4-dependent kinase; DSBs, double strand breaks; Dbf4, protein Dbf4 homolog A; Dfp1, Hsk1-Dfp1 kinase complex regulatory subunit Dfp1; Dpb11, DNA replication regulator Dpb11; E2F, E2F transcription factor; EL, early to late origins transition; ETG1, E2F target gene 1/replisome factor; Fkh, fork head domain protein; GCN5, histone acetyltransferase GCN5; GINS, go-ichi-ni-san; LE, late to early origins transition; MCM2–7, minichromosome maintenance helicase complex; NDT, N-terminus domain; ORC, origin recognition complex; ORCA, origin recognition complex subunit A; PCC, premature chromosome condensation; PCNA, proliferating cell nuclear antigen; RO, replication origin; RPD3, histone deacetylase 3; RTC, replication timing control; Rif1, replication timing regulatory factor 1; SCF, Skp1-Cullin-F-Box ligase; SIR, sulfite reductase; Sld2, replication regulator Sld2; Sld3, replication regulator Sld3; Swi6, chromatin-associated protein swi6; Taz1, telomere length regulator taz1; YKU70, yeast Ku protein.; dormant origins; mathematical models of replication; ori, origin; origin competence; origin efficiency; origin firing; origin licensing; p53, tumor suppressor protein p53; replication timing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Chromatin / chemistry
  • Chromatin / metabolism
  • DNA Replication*
  • Humans
  • Minichromosome Maintenance Proteins / metabolism
  • Models, Theoretical
  • Nuclear Proteins / metabolism
  • Replication Origin / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism


  • Cell Cycle Proteins
  • Chromatin
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Minichromosome Maintenance Proteins