Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

By J. Reynolds, L. Bicknell, P. Carroll, M. Higgs, R. Shaheen, J. Murray, D. Papadopoulos, A. Leitch, O. Murina, Zygimante Tarnauskaite and 52 more. 2017

100 citations recorded by the source corpus.

Subfields: Cancer Research, Cell Biology, Molecular Biology

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Citations in the corpus

• In silico protein interaction screening uncovers DONSON’s role in replication initiation (2023, background): “S18A) and result in partial loss of function by reducing protein levels ( 23 ).”
• Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome (2017, background): “Indeed, during review of this manuscript, Reynolds et al. (2017) published a series of cases of recessive, hypomorphic mutations in DONSON causing primary microcephaly, microcephaly with short stature, and MPD.”
• DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation (2023, methodology): “As DONSON was proposed to stabilise stalled replication forks in human cells ( 25 ), we next tested whether the inhibition of DNA replication in DONSON-depleted extract is due to the collapse of early replication forks, which could lead to S-phase checkpoint activation and inhibition of any further…”
• PRIM1 deficiency causes a distinctive primordial dwarfism syndrome (2020, unknown): “Heterozygous stabilizing mutations in GMNN and recessive variants in CDC45 , MCM5 , and DONSON have subsequently been associated with MGS (Burrage et al. 2015; Fenwick et al. 2016; Reynolds et al. 2017; Vetro et al. 2017).”
• DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in C. elegans (2023, unknown): “…initiation is deregulated during tumor development, as well as providing further mechanistic insight into how DNA replication initiation defects might underpin the development of human disease syndromes that are associated with mutations in DONSON (33, 34) and the SLD-2 orthologue RECQL4 (56, 57).”
• Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics (2020, background): “We have previously shown that a non-canonical splice-site variant in DONSON causes microcephalic primordial dwarfism when inherited in trans with a hypomorphic variant, but results in an embryonically lethal microcephaly-micromelia syndrome when homozygous [49].”
• The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome (2023, background): “DONSON is a replisome component and replication fork stabiliser that is involved in activating the ATR-dependent replication stress response [15].”
• Biallelic and De Novo Variants in DONSON Reveal a Clinical Spectrum of Cell Cycle-opathies with Microcephaly, Dwarfism and Skeletal Abnormalities (2019, background): “Most recently, biallelic mutations in DONSON have been identified in families with MPD phenotypes of varied severity and clinical description, including Microcephaly micromelia syndrome (MMS, OMIM 251230), Microcephaly, short stature, and limb abnormalities (MISSLA, OMIM 617604), and microcephalic p”