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Related Experiment Videos

The replication timing program in the hands of two HDACs.

Kazumasa Yoshida1, Armelle Lengronne2, Philippe Pasero2

  • 1Equipe Labellisée Ligue Contre le Cancer, Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France. ; Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Microbial Cell (Graz, Austria)
|March 31, 2017
PubMed
Summary

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Histone deacetylases Rpd3 and Sir2 oppositely regulate DNA replication timing in budding yeast. Epigenetic control of repetitive sequences, particularly in rDNA, is crucial for coordinating the replication program.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Yeast Genetics

Background:

  • Genomic DNA replication in eukaryotes relies on the coordinated firing of numerous replication origins.
  • Replication origins exhibit variations in initiation timing, chromatin organization, and nuclear positioning.
  • Histone deacetylases (HDACs) are critical regulators of gene expression and chromatin structure.

Purpose of the Study:

  • To systematically investigate the role of HDACs in regulating DNA replication origin activity in budding yeast.
  • To elucidate how epigenetic modifications influence the DNA replication program, particularly at repetitive sequences.
  • To understand the distinct contributions of Rpd3 and Sir2 to replication timing.

Main Methods:

  • Systematic analysis of histone deacetylase (HDAC) function in budding yeast.
Keywords:
DNA replicationbudding yeastepigeneticshistone deacetylases

Related Experiment Videos

  • Assessing the impact of Rpd3 and Sir2 on replication origin activity and timing.
  • Investigating epigenetic regulation of repetitive sequences, including the ribosomal DNA (rDNA) array.
  • Main Results:

    • Epigenetic regulation of repetitive sequences is a key determinant of the DNA replication program.
    • The HDACs Rpd3 and Sir2 exhibit opposing effects on replication timing.
    • Rpd3 delays initiation at late origins, while Sir2 promotes early origin activation.
    • Rpd3 and Sir2 regulate initiation at approximately 200 replication origins within the rDNA array.

    Conclusions:

    • Histone deacetylases Rpd3 and Sir2 play crucial, opposing roles in regulating the DNA replication timing program.
    • Epigenetic control of repetitive elements, especially rDNA, is vital for orchestrating replication.
    • Modulation of initiation factor availability by epigenetic regulation of repetitive origins likely controls replication timing.