Identification of 1600 replication origins in
DNA replication
Mcm
S. cerevisiae
chromosomes
gene expression
genetics
genomics
helicase
replication initiation
replication origin
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
05 Feb 2024
05 Feb 2024
Historique:
medline:
7
2
2024
pubmed:
5
2
2024
entrez:
5
2
2024
Statut:
epublish
Résumé
There are approximately 500 known origins of replication in the yeast genome, and the process by which DNA replication initiates at these locations is well understood. In particular, these sites are made competent to initiate replication by loading of the Mcm replicative helicase prior to the start of S phase; thus, 'a site that binds Mcm in G1' might be considered to provide an operational definition of a replication origin. By fusing a subunit of Mcm to micrococcal nuclease, we previously showed that known origins are typically bound by a single Mcm double hexamer, loaded adjacent to the ARS consensus sequence (ACS). Here, we extend this analysis from known origins to the entire genome, identifying candidate Mcm binding sites whose signal intensity varies over at least three orders of magnitude. Published data quantifying single-stranded DNA (ssDNA) during S phase revealed replication initiation among the most abundant 1600 of these sites, with replication activity decreasing with Mcm abundance and disappearing at the limit of detection of ssDNA. Three other hallmarks of replication origins were apparent among the most abundant 5500 sites. Specifically, these sites: (1) appeared in intergenic nucleosome-free regions flanked on one or both sides by well-positioned nucleosomes; (2) were flanked by ACSs; and (3) exhibited a pattern of GC skew characteristic of replication initiation. We conclude that, if sites at which Mcm double hexamers are loaded can function as replication origins, then DNA replication origins are at least threefold more abundant than previously assumed, and we suggest that replication may occasionally initiate in essentially every intergenic region. These results shed light on recent reports that as many as 15% of replication events initiate outside of known origins, and this broader distribution of replication origins suggest that S phase in yeast may be less distinct from that in humans than widely assumed.
Identifiants
pubmed: 38315095
doi: 10.7554/eLife.88087
pii: 88087
doi:
pii:
Substances chimiques
Nucleosomes
0
Saccharomyces cerevisiae Proteins
0
DNA, Intergenic
0
Cell Cycle Proteins
0
Banques de données
GEO
['GSE242131', 'GSE4099']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01GM117446
Pays : United States
Informations de copyright
© 2023, Foss et al.
Déclaration de conflit d'intérêts
EF, CL, TG, SG, BL, UL, AB No competing interests declared
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