Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early- And late-replicating euchromatin

Timothy Hoggard, Carolin A. Müller, Conrad A. Nieduszynski, Michael Weinreich, Catherine A. Fox

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

A eukaryotic chromosome relies on the function of multiple spatially distributed DNA replication origins for its stable inheritance. The spatial location of an origin is determined by the chromosomal position of an MCM complex, the inactive form of the DNA replicative helicase that is assembled onto DNA in G1-phase (also known as origin licensing). While the biochemistry of origin licensing is understood, the mechanisms that promote an adequate spatial distribution ofMCM complexes across chromosomes are not. We have elucidated a role for the Sir2 histone deacetylase in establishing the normal distribution of MCM complexes across Saccharomyces cerevisiae chromosomes. In the absence of Sir2, MCM complexes accumulated within both early-replicating euchromatin and telomeric heterochromatin, and replication activity within these regions was enhanced. Concomitantly, the duplication of several regions of late-replicating euchromatin were delayed. Thus, Sir2- mediated attenuation of origin licensing within both euchromatin and telomeric heterochromatin established the normal spatial distribution of origins across yeast chromosomes important for normal genome duplication.

Original languageEnglish
Pages (from-to)14314-14321
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number25
DOIs
Publication statusPublished - 23 Jun 2020

Keywords

  • Chromatin
  • Chromosomes
  • Origin licensing
  • Sir
  • Yeast

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