Chromosome instability caused by mutations in the genes involved in transcription and splicing

Sugaya, Kimihiko

doi:10.1080/15476286.2019.1652523

Cited by 10 publications

(6 citation statements)

References 49 publications

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“…Thus, loss of ik is also likely to induce genomic instability even in vivo leading to reduction of the ofd1 mRNA expression. This possibility is also further supported by recent report showing mutation of SMU1, which is a reciprocal interactor of IK and functions as a unit by stabilizing each other, results in chromosomal abnormality with aberrant sister chromatid exchanges [ 59 ]. They referred that defects of these splicing factors could disrupt links between RNA metabolism and genomic recombination, thereby leading to abnormal gene expression.…”

Section: Discussionsupporting

confidence: 54%

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene, ofd1

Ka,

Cho,

Kwon

et al. 2023

Cell Biosci

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Background The cilia are microtubule-based organelles that protrude from the cell surface. Abnormalities in cilia result in various ciliopathies, including polycystic kidney disease (PKD), Bardet-Biedl syndrome (BBS), and oral-facial-digital syndrome type I (OFD1), which show genetic defects associated with cilia formation. Although an increasing number of human diseases is attributed to ciliary defects, the functions or regulatory mechanisms of several ciliopathy genes remain unclear. Because multi ciliated cells (MCCs) are especially deep in vivo, studying ciliogenesis is challenging. Here, we demonstrate that ik is essential for ciliogenesis in vivo. Results In the absence of ik, zebrafish embryos showed various ciliopathy phenotypes, such as body curvature, abnormal otoliths, and cyst formation in the kidney. RNA sequencing analysis revealed that ik positively regulated ofd1 expression required for cilium assembly. In fact, depletion of ik resulted in the downregulation of ofd1 expression with ciliary defects, and these ciliary defects in ik mutants were rescued by restoring ofd1 expression. Interestingly, ik affected ciliogenesis particularly in the proximal tubule but not in the distal tubule in the kidney. Conclusions This study demonstrates the role of ik in ciliogenesis in vivo for the first time. Loss of ik in zebrafish embryos displays various ciliopathy phenotypes with abnormal ciliary morphology in ciliary tissues. Our findings on the ik–ofd1 axis provide new insights into the biological function of ik in clinical ciliopathy studies in humans.

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Section: Discussionsupporting

confidence: 54%

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene, ofd1

Ka,

Cho,

Kwon

et al. 2023

Cell Biosci

View full text Add to dashboard Cite

show abstract

“…Thus, loss of ik is also likely to induce genomic instability even in vivo leading to reduction of the ofd1 mRNA expression. This possibility is also further supported by recent report showing mutation of SMU1, reciprocal interactor of IK to function as a unit by stabilizing each other, resulted in chromosomal abnormality with aberrant sister chromatid exchanges [60]. They referred that defects of these splicing factors affect links between RNA metabolism and replication resulting in genomic recombination and result in the abnormal gene expression.…”

Section: Discussionmentioning

confidence: 59%

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1

Cho

Kwon

et al. 2023

Preprint

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Background The cilia are microtubule-based organelles that protrude from the cell surface. Abnormalities in cilia result in various ciliopathies, including polycystic kidney disease (PKD), Bardet-Biedl syndrome (BBS), and oral-facial-digital syndrome type I (OFD1), which show genetic defects associated with cilia formation. Although an increasing number of human diseases is attributed to ciliary defects, the functions or regulatory mechanisms of several ciliopathy genes remain unclear. Because cilia are deep in vivo, studying ciliogenesis is challenging. Here, we demonstrate that IK is essential for ciliogenesis in vivo. Results In the absence of IK, zebrafish embryos showed various ciliopathy phenotypes, such as body curvature, abnormal otoliths, and cyst formation in the kidney. RNA sequencing analysis showed that IK positively regulated ofd1 expression required for cilium assembly. Downregulation of ofd1 expression upon depletion of IK led to ciliary defects that was rescued by restoration of ofd1 expression. Interestingly, IK affected ciliogenesis particularly in the proximal tubule but not in the distal tubule in the kidney. Conclusions This study demonstrates the role of IK in ciliogenesis in vivo for the first time. Loss of IK in zebrafish embryos displays various ciliopathy phenotypes with abnormal ciliary morphology in ciliary tissues. Our findings on the IK–OFD1 axis provide new insights into the biological function of IK in clinical ciliopathy studies in humans.

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“…DNA strand breaks and repair are common events in human cells. In any metaphase plate, several sister chromatid exchanges are usually seen [ 28 ]. This is a result of errors in DNA repair.…”

Section: Resultsmentioning

confidence: 99%

The Precise Breakpoint Mapping in Paracentric Inversion 10q22.2q23.3 by Comprehensive Cytogenomic Analysis, Multicolor Banding, and Single-Copy Chromosome Sequencing

et al. 2022

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Detection and precise genomic mapping of balanced chromosomal abnormalities in patients with impaired fertility or a clinical phenotype represent a challenge for current cytogenomics owing to difficulties with precise breakpoint localization in the regions enriched for DNA repeats and high genomic variation in such regions. Here, we present a comprehensive cytogenomic approach to breakpoint mapping in a rare paracentric inversion on 10q (in a patient with oligoasthenoteratozoospermia and necrozoospermia) that does not affect other phenotype traits. Multicolor banding, chromosomal microarray analysis, chromosome microdissection with reverse painting, and single-copy sequencing of the rearranged chromosome were performed to determine the length and position of the inverted region as well as to rule out a genetic imbalance at the breakpoints. As a result, a paracentric 19.251 Mbp inversion at 10q22.2q23.3 was described. The most probable location of the breakpoints was predicted using the hg38 assembly. The problems of genetic counseling associated with enrichment for repeats and high DNA variability of usual breakpoint regions were discussed. Possible approaches for cytogenomic assessment of couples with balanced chromosome rearrangements and problems like reproductive failures were considered and suggested as useful part of effective genetic counseling.

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Chromosome instability caused by mutations in the genes involved in transcription and splicing

Cited by 10 publications

References 49 publications

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene, ofd1

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene, ofd1

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1

The Precise Breakpoint Mapping in Paracentric Inversion 10q22.2q23.3 by Comprehensive Cytogenomic Analysis, Multicolor Banding, and Single-Copy Chromosome Sequencing

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