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Cited by 49DNA Repair MechanismsMicrotubule and mitosis dynamicsFungal and yeast genetics research

Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome Integrity

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Kottemann, Molly C., Conti, Brooke A., Lach, Francis P., Smogorzewska, Agata·2018·Molecular Cell
DOI 10.1016/j.molcel.2017.11.035PMC PMC6467090
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Abstract

The protection and efficient restart of stalled replication forks is critical for the maintenance of genome integrity. Here, we identify a regulatory pathway that promotes stalled forks recovery from replication stress. We show that the mammalian replisome component C20orf43/RTF2 (homologous to S. pombe Rtf2) must be removed for fork restart to be optimal. We further show that the proteasomal shuttle proteins DDI1 and DDI2 are required for RTF2 removal from stalled forks. Persistence of RTF2 at stalled forks results in fork restart defects, hyperactivation of the DNA damage signal, accumulation of single-stranded DNA (ssDNA), sensitivity to replication drugs, and chromosome instability. These results establish that RTF2 removal is a key determinant for the ability of cells to manage replication stress and maintain genome integrity.

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  • In S. Pombe, removal of RTFDC1 (RTF2) from stalled replication forks during S phase DNA replication is essential to maintain replication stress and genome integrity.

    “What is known to date is that in S. Pombe the removal of RTFDC1 (also known as RTF2) from stalled replication forks during S phase DNA replication is essential to maintain replication stress and genome integrity69.”

    From Variant-to-function mapping of late-onset Alzheimer’s disease GWAS signals in human microglial cell models implicates <i>RTFDC1</i> at the <i>CASS4</i> locus (2024) · cites this paper as [69]

    The Abstract and Discussion identify removal of RTF2 from stalled forks as a protective process in mammalian or human cells, not S. pombe. The Results section on DDI1/2 instead says S. pombe Rtf2 is required to maintain fork stalling at a specific replication termination site. Page numbers were not provided. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Kottemann, M. C., Conti, B. A., Lach, F. P., & Smogorzewska, A.
Affiliations
Rockefeller University (US)
Corresponding author
Smogorzewska, Agata
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2018-01
Volume
69
Issue
1
Pages
24-35.e5
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2017.11.035
PMC
PMC6467090
OpenAlex
W2776494444
Cited by
49
References
7
Citations by year
2026: 2 · 2025: 2 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 13 · 2019: 4 · 2018: 3
FWCI
2.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Rockefeller University
  • American Cancer Society
  • NIH (#GM066699)
  • Pershing Square Sohn Prize for Young Investigators in Cancer Research
  • The Gabrielle H. Reem and Herbert J. Kayden Early-Career Innovation Award
  • HHMI
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
replication fork restart, stalled replication forks, replisome, replication stress, genome stability, proteasome, Ddi1, DDI2, DNA damage response, single-stranded DNA, chromosomal instability
MeSH terms
Cell Cycle, DNA, DNA Damage, DNA Repair, DNA Replication, DNA-Binding Proteins, DNA, Single-Stranded, HeLa Cells, Humans, Stress, Physiological, Replication Origin, Cell Cycle Proteins, RNA Interference, RNA, Small Interfering, Genomic Instability, Cell Line, Tumor, Aspartic Acid Proteases

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