Cited by 65DNA Repair MechanismsFungal and yeast genetics researchBacterial Genetics and Biotechnology

Yeast Rev1 is cell cycle regulated, phosphorylated in response to DNA damage and its binding to chromosomes is dependent upon MEC1

Sabbioneda, Simone, Bortolomai, Ileana, Giannattasio, Michele, Plevani, Paolo, Muzi-Falconi, Marco·2007·DNA Repair

Abstract

Translesion DNA synthesis (TLS) is one of the mechanisms involved in lesion bypass during DNA replication. Three TLS polymerases (Pol) are present in the yeast Saccharomyces cerevisiae: Pol zeta, Pol eta and the product of the REV1 gene. Rev1 is considered a deoxycytidyl transferase because it almost exclusively inserts a C residue in front of the lesion. Even though REV1 is required for most of the UV-induced and spontaneous mutagenesis events, the role of Rev1 is poorly understood since its polymerase activity is often dispensable. Rev1 interacts with several TLS polymerases in mammalian cells and may act as a platform in the switching mechanism required to substitute a replicative polymerase with a TLS polymerase at the sites of DNA lesions. Here we show that yeast Rev1 is a phosphoprotein, and the level of this modification is cell cycle regulated under normal growing conditions. Rev1 is unphosphorylated in G1, starts to be modified while cells are passing S phase and it becomes hyper-phosphorylated in mitosis. Rev1 is also hyper-phosphorylated in response to a variety of DNA damaging agents, including treatment with a radiomimetic drug mostly causing double-strand breaks (DSB). By using the chromosome spreading technique we found the Rev1 is bound to chromosomes throughout the cell cycle, and its binding does not significantly increase in response to genotoxic stress. Therefore, Rev1 phosphorylation does not appear to modulate its binding to chromosomes, suggesting that such modification may influence other aspects of the TLS process. Rev1 binding under damaged and undamaged conditions, is at least partially dependent on MEC1, a gene playing a pivotal role in the DNA damage checkpoint cascade. This genetic dependency may suggest a role for MEC1 in spontaneous mutagenesis events, which require a functional REV1 gene.

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Crossref · 10.1016/j.dnarep.2006.09.002

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  • An active checkpoint leads to Rev1 phosphorylation, possibly increasing TLS activity and reducing RPA-covered ssDNA, promoting checkpoint switch-off.

    “An active checkpoint leads to Rev1 phosphorylation [86,87], possibly increasing TLS activity and progressively reducing the amount of RPA-covered ssDNA, thus promoting the switch off of the checkpoint itself.”

    From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [87]

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Authors
Sabbioneda, S., Bortolomai, I., Giannattasio, M., Plevani, P., & Muzi-Falconi, M.
Affiliations
University of Milan (IT)
Corresponding author
  • Plevani, Paolo
  • Muzi-Falconi, Marco
Venue
DNA Repair
Publisher
Elsevier BV
Published
2007-01
Volume
6
Issue
1
Pages
121-127
ISSN
  • 1568-7856 (ISSN-L)
  • 1568-7864
OpenAlex
W2072289417
Cited by
65
References
43
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 4 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 1 · 2013: 8 · 2012: 5
FWCI
2.58
Type
journal article
Language
en
Open access
closed
Locations
  • DNA repair (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • European Commission
  • Associazione Italiana per la Ricerca sul Cancro
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Rev1, translesion synthesis, DNA damage response, phosphorylation, cell cycle regulation, Mec1, DNA damage checkpoint, UV mutagenesis, spontaneous mutagenesis, Saccharomyces cerevisiae, DNA double-strand breaks, radiomimetic agents
MeSH terms
Y-Family DNA Polymerases, DNA Damage, DNA-Directed DNA Polymerase, DNA Repair, DNA, Fungal, Mitosis, Nucleotidyltransferases, Phosphoproteins, Phosphorylation, Saccharomyces cerevisiae, Chromosomes, Fungal, G1 Phase, S Phase, Protein Serine-Threonine Kinases, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins

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