Evidence map›Paper›PMID 41719335›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

A Meier-Gorlin syndrome mutation impairs the loading of the MCM2-7 complex during DNA replication initiation.

Yusong Liu, Mengquan Yang, Ping Lu, Haishan Gao, Maozhou He, Yitao Wang, Ao Qi, Ting Cao, Qiuqin Zhang, Shutao Qi and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Yusong Liu *School of Life Sciences, Fudan University, Shanghai 200433, China.ORCID 0009-0000-1926-3503
Mengquan Yang *School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.ORCID 0000-0001-5338-8318
Ping Lu *School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.
Haishan GaoSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.
Maozhou HeSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.
Yitao WangSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.
Ao QiSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.
Ting CaoSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.
Qiuqin ZhangSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.
Shutao QiSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.ORCID 0000-0002-4073-1161
Yigong ShiSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.
Hongtao YuSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China.ORCID 0000-0002-8861-049X

Funding

MOST | National Natural Science Foundation of China (NSFC) 32130053
6 · The paper itself

Abstract

Chromatin loading of the hexameric replicative helicase MCM2-7 complex requires coordinated interactions with the origin recognition complex (ORC), CDC6, and CDT1. MCM2-7 not bound to DNA forms a single hexamer (SH) with an open DNA entry gate between MCM2 and MCM5. Two MCM2-7 SHs can be loaded sequentially to form the double hexamer (DH) that encircles the DNA duplex. Activated MCM2-7 then unwinds DNA and initiates DNA replication. Our cryoelectron microscopy analyses show that a fraction of human MCM2-7 without DNA exists as DH. Unexpectedly, we find that the MCM3 winged helix domain (WHD) docks on MCM2 in both DNA-free DH and SH, creating a safety latch across the DNA entry gate to block DNA entry into the central channel. The safety latch can be opened by ORC-CDC6 binding. Perturbing this latch by structure-based or disease-related mutations of MCM3 causes replication defects and DNA damage checkpoint activation. Shortening the MCM3 linker between the helicase domain and WHD alleviates the cell cycle defects of the latch-strengthening mutation. Our findings uncover a regulated step in MCM2-7 loading with implications for human diseases.

Indexed as

Congenital MicrotiaDNA ReplicationMicrognathismMinichromosome Maintenance Complex Component 2Minichromosome Maintenance ProteinsMutationCell Cycle ProteinsCryoelectron MicroscopyGrowth DisordersHumansMinichromosome Maintenance Complex Component 3Minichromosome Maintenance Complex Component 7Nuclear ProteinsOrigin Recognition ComplexPatellaProtein BindingCDC6 protein, humanCell Cycle ProteinsMCM2 protein, humanMCM3 protein, humanMCM7 protein, humanMinichromosome Maintenance Complex Component 2Minichromosome Maintenance Complex Component 3Minichromosome Maintenance Complex Component 7Minichromosome Maintenance ProteinsNuclear ProteinsOrigin Recognition ComplexDNA replicationhelicaseMeier–Gorlin syndromewinged helix domain

Identifiers

PMID41719335
PMCPMC12933075

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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.