Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund–Thomson syndrome

Yokoyama, Hideki; Moreno-Andrés, Daniel; Astrinidis, Susanne Adina; Hao, Yuqing; Weberruß, Marion; Schellhaus, Anna Katharina; Lue, Hongqi; Haramoto, Yoshikazu; Gruß, Oliver J.; Antonin, Wolfram

doi:10.26508/lsa.201800120

Cited by 19 publications

(37 citation statements)

References 53 publications

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“…Incubation of sperm chromatin in egg extracts and chromatin re-isolation showed that Xenopus VPS72 bound to chromatin in interphase but not in mitosis ( Figure 2 B). CAP-G, a component of the condensin complex, behaved expectedly the opposite way [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…Recombinant human histone H2A.Z-H2B dimer (Millipore, Darmstadt, Germany) was added to the nuclear assembly at 0.3 µM. To monitor DNA replication, the egg extract was supplemented with 5 µM Cy3-labeled dUTP (Roche, Basel, Switzerland) and used for nuclear assembly [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

“…Cytostatic factor (CSF)-arrested Xenopus egg extract was prepared as described previously [32]. The extract was incubated in the presence or absence of 1250 sperm/µL and 0.4 mM CaCl 2 .…”

Section: Chromatin Re-isolationmentioning

confidence: 99%

“…To monitor DNA replication, the egg extract was supplemented with 5 µM Cy3-labeled dUTP (Roche, Basel, Switzerland) and used for nuclear assembly [32].…”

Section: Nuclear Assembly Assay and Chromatin De-condensation Assaymentioning

confidence: 99%

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VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis

Moreno-Andrés

Yokoyama

Scheufen

et al. 2020

Cells

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The eukaryotic nucleus remodels extensively during mitosis. Upon mitotic entry, the nuclear envelope breaks down and chromosomes condense into rod-shaped bodies, which are captured by the spindle apparatus and segregated during anaphase. Through telophase, chromosomes decondense and the nuclear envelope reassembles, leading to a functional interphase nucleus. While the molecular processes occurring in early mitosis are intensively investigated, our knowledge about molecular mechanisms of nuclear reassembly is rather limited. Using cell free and cellular assays, we identify the histone variant H2A.Z and its chaperone VPS72/YL1 as important factors for reassembly of a functional nucleus after mitosis. Live-cell imaging shows that siRNA-mediated downregulation of VPS72 extends the telophase in HeLa cells. In vitro, depletion of VPS72 or H2A.Z results in malformed and nonfunctional nuclei. VPS72 is part of two chromatin-remodeling complexes, SRCAP and EP400. Dissecting the mechanism of nuclear reformation using cell-free assays, we, however, show that VPS72 functions outside of the SRCAP and EP400 remodeling complexes to deposit H2A.Z, which in turn is crucial for formation of a functional nucleus.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Cytostatic factor (CSF)-arrested Xenopus egg extract was prepared as described previously [32]. The extract was incubated in the presence or absence of 1250 sperm/µL and 0.4 mM CaCl 2 .…”

Section: Chromatin Re-isolationmentioning

confidence: 99%

“…To monitor DNA replication, the egg extract was supplemented with 5 µM Cy3-labeled dUTP (Roche, Basel, Switzerland) and used for nuclear assembly [32].…”

Section: Nuclear Assembly Assay and Chromatin De-condensation Assaymentioning

confidence: 99%

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VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis

Moreno-Andrés

Yokoyama

Scheufen

et al. 2020

Cells

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“…The RECQL4 protein participates in HR and NHEJ DSB repair [155,156] and telomere maintenance [157]. Its roles in origin activation during the S-phase and chromosome alignment during replication were also described [158][159][160][161]. Different mice models of Recql4 inactivation have been generated, but no CNS phenotypes were found [162][163][164].…”

Section: Recql4mentioning

confidence: 99%

Protective Mechanisms Against DNA Replication Stress in the Nervous System

Charlier

Martins

2020

Genes

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The precise replication of DNA and the successful segregation of chromosomes are essential for the faithful transmission of genetic information during the cell cycle. Alterations in the dynamics of genome replication, also referred to as DNA replication stress, may lead to DNA damage and, consequently, mutations and chromosomal rearrangements. Extensive research has revealed that DNA replication stress drives genome instability during tumorigenesis. Over decades, genetic studies of inherited syndromes have established a connection between the mutations in genes required for proper DNA repair/DNA damage responses and neurological diseases. It is becoming clear that both the prevention and the responses to replication stress are particularly important for nervous system development and function. The accurate regulation of cell proliferation is key for the expansion of progenitor pools during central nervous system (CNS) development, adult neurogenesis, and regeneration. Moreover, DNA replication stress in glial cells regulates CNS tumorigenesis and plays a role in neurodegenerative diseases such as ataxia telangiectasia (A-T). Here, we review how replication stress generation and replication stress response (RSR) contribute to the CNS development, homeostasis, and disease. Both cell-autonomous mechanisms, as well as the evidence of RSR-mediated alterations of the cellular microenvironment in the nervous system, were discussed.

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Rothmund–Thomson syndrome type 1 caused by biallelic ANAPC1 gene mutations

Zirn

Bernbeck

Alt

et al. 2021

Skin Health and Disease

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Background Rare syndromic skin disorders may represent a diagnostic challenge. Aims We report a unique case associating cutaneous manifestations and developmental delay. Materials & Methods The affected 14 months old boy had poikiloderma, facial dysmorphism with deep‐set eyes, atrichia, as well as nail dysplasia and non‐descended testes. In addition, his psychomotor development was delayed. Exome sequencing and molecular karyotyping via array‐CGH (oligo‐array, 180k Agilent, design 22060) were performed. Results Mutations in RECQL4 (found in patients with RTS2) were first excluded. In the ANAPC1 gene, a novel combination of a recurrent intronic mutation (c.2705‐198C>T) and a deletion of the second ANAPC1 allele was detected, thus confirming the clinical diagnosis of RTS1. The deletion on chromosome 2q13 comprised further genes and spanned 1,7 megabases. Heterozygous deletions in this region are known as 2q13 microdeletion syndrome and are associated with developmental delay, autism and facial dysmorphism. Discussion The genetic findings most probably explain both, the RTS1 features and the developmental delay. Genetic diagnosis in RTS is indispensable to confirm the specific subtype and its associated risks: juvenile cataracts are features of RTS1 (ANAPC1 gene), whereas a high risk of osteosarcoma is part of RTS2 (RECQL4 gene). Thus, the patient described here is at high risk for the development of juvenile cataracts and requires regular ophthalmologic examination. Conclusion This case report underlines the necessity of thorough clinical diagnosis prior to genetic diagnosis of RTS1, since the recurrent intronic ANAPC1 mutation is otherwise missed.

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Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund–Thomson syndrome

Abstract: RECQL4, which is mutated in the Rothmund–Thomson syndrome characterized by premature aging and cancer susceptibility, is a microtubule-associated protein required for mitotic chromosome alignment.

Cited by 19 publications

References 53 publications

VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis

VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis

Protective Mechanisms Against DNA Replication Stress in the Nervous System

Rothmund–Thomson syndrome type 1 caused by biallelic ANAPC1 gene mutations

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