Cited by 45DNA Repair MechanismsNuclear Structure and FunctionDNA and Nucleic Acid Chemistry

Coordinated Activity of Y Family TLS Polymerases and EXO1 Protects Non-S Phase Cells from UV-Induced Cytotoxic Lesions

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Sertic, Sarah, Mollica, Antonio, Campus, Ilaria, Roma, Stefania, Tumini, Emanuela, Aguilera, Andrés, Muzi-Falconi, Marco·2018·Molecular Cell

Abstract

UV-induced photoproducts are responsible for the pathological effects of sunlight. Mutations in nucleotide excision repair (NER) cause severe pathologies characterized by sunlight sensitivity, coupled to elevated predisposition to cancer and/or neurological dysfunctions. We have previously shown that in UV-irradiated non-cycling cells, only a particular subset of lesions activates the DNA damage response (DDR), and this requires NER and EXO1 activities. To define the molecular mechanism acting at these lesions, we demonstrate that Y family TLS polymerases are recruited at NER- and EXO1-positive lesion sites in non-S phase cells. The coordinated action of EXO1 and Y family TLS polymerases promotes checkpoint activation, leads to lesion repair, and is crucial to prevent cytotoxic double-strand break (DSB) formation.

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Crossref · 10.1016/j.molcel.2018.02.017

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  • In eukaryotic cells, interaction of polymerases with PCNA, dependent on its ubiquitination status, seems crucial for employment of TLS polymerases for lesion bypass.

    “In eukaryotic cells interaction of polymerases with PCNA (dependent on its ubiquitination status) seems to be crucial for employment of TLS polymerases for lesion bypass [127,129].”

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Authors
Sertic, S., Mollica, A., Campus, I., Roma, S., Tumini, E., Aguilera, A., & Muzi-Falconi, M.
Affiliations
  • University of Milan (IT)
  • Consejo Superior de Investigaciones Científicas (ES)
Corresponding author
  • Sertic, Sarah
  • Muzi-Falconi, Marco
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2018-04
Volume
70
Issue
1
Pages
34-47.e4
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2790495781
Cited by
45
References
68
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 10 · 2019: 5 · 2018: 1
FWCI
1.69
Type
journal article
Language
en
Update notices
erratum (2018-04-05)
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
  • Fondazione Umberto Veronesi
  • AIRC (15631)
  • Telethon (GGP15227)
  • MIUR
  • Spanish Ministry of Economy and Competitiveness (BFU2016-75058-P)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
EXO1, nucleotide excision repair, DNA damage response, double-strand break formation, DNA repair, checkpoint activation, UV sensitivity
MeSH terms
DNA Polymerase iota, Y-Family DNA Polymerases, Cell Line, DNA-Directed DNA Polymerase, DNA Repair, Exodeoxyribonucleases, Humans, Nuclear Proteins, Nucleotidyltransferases, Ultraviolet Rays, Cell Death, Protein Transport, DNA Repair Enzymes, DNA Breaks, Double-Stranded, Cell Cycle Checkpoints

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