Evidence map›Paper›PMID 30476303›Full record

ArticleNucleic acids research2019

Mrc1 and Tof1 prevent fragility and instability at long CAG repeats by their fork stabilizing function.

Lionel Gellon, Simran Kaushal, Jorge Cebrián, Mayurika Lahiri, Sergei M Mirkin, Catherine H Freudenreich

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. The TIMELESS effort for timely DNA replication and protection.Cellular and molecular life sciences : CMLS · 2023
    Review
  10. Article
  11. Article
  12. Article
  13. Homologous recombination within repetitive DNA.Current opinion in genetics & development · 2021
    Review
  14. Article
  15. Article
  16. Article
  17. The intra-S phase checkpoint directly regulates replication elongation to preserve the integrity of stalled replisomes.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Lionel GellonDepartment of Biology, Tufts University, Suite 4700, 200 Boston Ave, Medford, MA 02155, USA.
Simran KaushalDepartment of Biology, Tufts University, Suite 4700, 200 Boston Ave, Medford, MA 02155, USA.
Jorge CebriánDepartment of Biology, Tufts University, Suite 4700, 200 Boston Ave, Medford, MA 02155, USA.
Mayurika LahiriDepartment of Biology, Tufts University, Suite 4700, 200 Boston Ave, Medford, MA 02155, USA.
Sergei M MirkinDepartment of Biology, Tufts University, Suite 4700, 200 Boston Ave, Medford, MA 02155, USA.
Catherine H FreudenreichDepartment of Biology, Tufts University, Suite 4700, 200 Boston Ave, Medford, MA 02155, USA.
Tufts University · US

Funding

REPLICATION OF SIMPLE DNA REPEATSR01GM060987 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MIRKIN, SERGEI · 2001 to 2017
$4.9M
NIGMS Equipment SupplementR35GM130322 · NIGMS · TUFTS UNIVERSITY MEDFORD · PI SERGEI MIRKIN · 2019 to 2026
$4.6M
Fork Restart at Replication Barriers and Effects on Genome StabilityR01GM122880 · NIGMS · TUFTS UNIVERSITY MEDFORD · PI FREUDENREICH, CATHERINE H · 2017 to 2020
$1.4M
NIGMS NIH HHS R01 GM060987NIGMS NIH HHS R01 GM122880NIGMS NIH HHS R35 GM130322
6 · The paper itself

Abstract

Fork stabilization at DNA impediments is key to maintaining replication fork integrity and preventing chromosome breaks. Mrc1 and Tof1 are two known stabilizers that travel with the replication fork. In addition to a structural role, Mrc1 has a DNA damage checkpoint function. Using a yeast model system, we analyzed the role of Mrc1 and Tof1 at expanded CAG repeats of medium and long lengths, which are known to stall replication forks and cause trinucleotide expansion diseases such as Huntington's disease and myotonic dystrophy. We demonstrate that the fork stabilizer but not the checkpoint activation function of Mrc1 is key for preventing DNA breakage and death of cells containing expanded CAG tracts. In contrast, both Mrc1 functions are important in preventing repeat length instability. Mrc1 has a general fork protector role that is evident at forks traversing both repetitive and non-repetitive DNA, though it becomes crucial at long CAG repeat lengths. In contrast, the role of Tof1 in preventing fork breakage is specific to long CAG tracts of 85 or more repeats. Our results indicate that long CAG repeats have a particular need for Tof1 and highlight the importance of fork stabilizers in maintaining fork integrity during replication of structure-forming repeats.

Indexed as

Chromosome FragilityTrinucleotide RepeatsCell Cycle ProteinsDNA-Binding ProteinsDNA ReplicationGene DeletionSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCell Cycle ProteinsDNA-Binding ProteinsMRC1 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsTOF1 protein, S cerevisiae

Identifiers

PMID30476303
PMCPMC6344861
OpenAlexW2901420230

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.