Evidence map›Paper›PMID 41331242›Full record

ArticleNature communications2025

Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.

Xiaoxuan Zhu, Atabek Bektash, Yuki Hatoyama, Sachiko Muramatsu, Shin-Ya Isobe, Chikashi Obuse, Atsushi Toyoda, Yasukazu Daigaku, Chun-Long Chen, Masato T Kanemaki

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

10 authors.

Xiaoxuan ZhuDepartment of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan.ORCID http://orcid.org/0000-0002-1664-8034
Atabek BektashDepartment of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan.
Yuki HatoyamaDepartment of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan.ORCID http://orcid.org/0000-0001-5554-8311
Sachiko MuramatsuDepartment of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan.ORCID http://orcid.org/0009-0005-6512-7832
Shin-Ya IsobeDepartment of Biological Sciences, Graduate School of Science, The University of Osaka, Toyonaka, Osaka, Japan.
Chikashi ObuseDepartment of Biological Sciences, Graduate School of Science, The University of Osaka, Toyonaka, Osaka, Japan.
Atsushi ToyodaDepartment of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan.ORCID http://orcid.org/0000-0002-0728-7548
Yasukazu DaigakuCancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.ORCID http://orcid.org/0000-0002-8404-7492
Chun-Long ChenInstitut Curie, Université PSL, Sorbonne Université, CNRS UMR3244, Paris, France.ORCID http://orcid.org/0000-0002-4795-0295
Masato T KanemakiDepartment of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan. mkanemak@nig.ac.jp.ORCID http://orcid.org/0000-0002-7657-1649

Funding

Japan Agency for Medical Research and Development (AMED) JP25jf0126015MEXT | Japan Science and Technology Agency (JST) JPMJFR204XMEXT | Japan Society for the Promotion of Science (JSPS) JP21H04719MEXT | Japan Society for the Promotion of Science (JSPS) JP22H04925MEXT | Japan Society for the Promotion of Science (JSPS) JP23H02463MEXT | Japan Society for the Promotion of Science (JSPS) JP23H04925MEXT | Japan Society for the Promotion of Science (JSPS) JP25H00979MEXT | JST | Core Research for Evolutional Science and Technology (CREST) JPMJCR21E6
6 · The paper itself

Abstract

Replication origins in human cells form clusters ranging from tens to hundreds of kilobases called initiation zones (IZs), typically located in intergenic regions between active genes. On a larger megabase scale, chromosomes replicate following temporally defined replication timing (RT), where euchromatic regions replicate early, and heterochromatic regions replicate late. Although the stochastic model of IZ firing with a temporally regulated limiting factor can explain RT formation, this limiting factor in human cells remains unclear. To investigate the relationship between IZ and RT, we map the temporal firing pattern of IZs and examine the genome-wide distributions of replication licensing and firing factors in human cells. We identify TRESLIN-MTBP as a key limiting firing factor for replication initiation. Its loading onto phosphorylated MCM2-7 double hexamer (MCM-DH) is controlled by the opposing phosphorylation events on MCM-DH by Dbf4-dependent kinase and RIF1-Protein Phosphatase 1, which ultimately determine IZs and establish RT.

Indexed as

Cell Cycle ProteinsDNA ReplicationDNA Replication TimingHeLa CellsHumansMinichromosome Maintenance Complex Component 2Minichromosome Maintenance Complex Component 7Minichromosome Maintenance ProteinsPhosphorylationProtein Phosphatase 1Replication OriginTelomere-Binding ProteinsCell Cycle ProteinsMinichromosome Maintenance Complex Component 2Minichromosome Maintenance Complex Component 7Minichromosome Maintenance ProteinsProtein Phosphatase 1Rif1 protein, humanTelomere-Binding Proteins

Identifiers

PMID41331242
PMCPMC12672787

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Registered trials

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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.