Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down Syndrome brain

Shim, Ki Shuk; Bergelson, Jeffrey M.; Furuse, Mikio; Ovod, Vladimir; Krude, Torsten; Lubec, Gert

doi:10.1007/978-3-7091-6721-2_10

Cited by 22 publications

(23 citation statements)

References 36 publications

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“…Interleukin-1 is a non-chromosome-21-based cytokine that is also overexpressed throughout life in Down syndrome (19). Thus, these data reveal a complex regulation of gene expression that is not only related to gene copy number (15,20). Present work shows, however, a clear difference of DS patients from the controls in RNA content of PBMNCs.…”

Section: Discussionmentioning

confidence: 54%

“…In fact, overexpression of genes located on chromosome 21, as a result of extra gene load, has been considered a central hypothesis for the explanation of the DS phenotype (15). However, not all genes show the expected 50% increase in expression in the DS model of mice, and some genes show age-dependent changes in expression levels (15,16). Quantification of some proteins encoded on chromosome 21 revealed that not all gene products of the DS critical region are overexpressed in DS brain early in life, indicating that the DS phenotype cannot be simply explained by the gene dosage effect hypothesis (17,18).…”

Section: Discussionmentioning

confidence: 98%

“…The Down syndrome (DS) region on chromosome 21, which is responsible for the DS main features, has been defined by the analysis of DS patients with partial trisomy 21 (4) and transchromosomal mice (5). Human NORs (rDNA) have been localized at the secondary constriction on the five pairs (13)(14)(15)21, and 22) of acrocentric chromosomes (6). The genes coding for 5.8 s, 18 s, and 28 s ribosomal RNA (rRNA) have been localized in these regions (7).…”

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confidence: 99%

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Flow cytometric comparison of RNA content in peripheral blood mononuclear cells of down syndrome patients and control individuals

Hamurcu

Demirtaş

Kumandaş

2005

Cytometry Part B Clinical

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Objective: Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation associated with the immunologic and other known defects. Extra chromosome 21 of DS patients contains an average of 40 extra copies of rRNA genes and the in vivo regulation of these genes' activity is not known. Because over 80% of total cellular RNA is rRNA, the measurement of total cellular RNA provides information on rRNA content. The aim of this work was to determine whether or not the additional chromosome 21 causes any increase in total cellular RNA content in mononuclear cells from peripheral blood (PBMNCs) of these patients and whether or not this content is modified with age.Method: PBMNCs of 48 patients with DS and 48 healthy controls were studied. RNA content of isolated PBMNCs was evaluated by flow cytometric measurements.Results: Average RNA content of younger DS patients' cells was significantly higher than that of healthy controls (P = 0.003). Furthermore, the RNA content decreased significantly with increasing age of DS patients (r = -0.377, P = 0.008) in the range of 0-26 year old, whereas no significant relationship was found between age and PBMNCs' RNA content of healthy controls in the same range of ages.Conclusion: RNA content of PBMNCs from DS patients decreases rapidly with age. This is the first work on the age-dependent decrease of the RNA content in PBMNCs of DS patients. q 2005 International Society for Analytical Cytology

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Flow cytometric comparison of RNA content in peripheral blood mononuclear cells of down syndrome patients and control individuals

Hamurcu

Demirtaş

Kumandaş

2005

Cytometry Part B Clinical

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“…In fact, overexpression of genes located on chromosome 21, as a result of extra gene load, has been considered a central hypothesis for the explanation of the DS phenotype (17)(18)(19). However, not all genes show the expected 50% increase in expression in DS (18,19) and in mouse model of DS (1,20).…”

Section: Discussionmentioning

confidence: 99%

Age‐dependent decreases in mitogen‐stimulation level and RNA content in peripheral blood mononuclear cells of down syndrome patients

Hamurcu

Demirtaş

Patıroğlu

et al. 2006

Cytometry Part B Clinical

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Objective: The aim of the present study was to determine whether or not the phytohemagglutinin (PHA)-activated proliferation and average RNA content in peripheral blood mononuclear cells (PBMC) of Down syndrome (DS) patients change with age.Method: Stimulated portion of PBMC and total RNA levels in these cells after 72 h of PHA stimulation from 38 DS patients were compared with 28 age-matched healthy controls using flow cytometric measurement.Results: Decreased ratio of PBMC from DS patients undergoes mitogenic stimulation with age (r = À0.84, P = 0.000). This decrease is not observed in the cells of control individuals (r = 0.03, P = 0.869). Stimulated PBMC in infants with DS have higher level of RNA contents compared to controls (Z = 2.227, P = 0.026). While RNA content in mitogen-stimulated PBMC of DS decreased progressively and significantly with age (r = À0.70, P = 0.000), no significant age-related change in RNA content was found among the cells of healthy individuals in the range of 0-27 year old (r = 0.275, P = 0.157, P > 0.05).Conclusion: Age-dependent decreases in mitogen-activated proliferation ratio and average RNA content of PBMC from DS patients appear as regular events. These results may contribute to the explanation of the immune deficiency seen in DS patients since the PHA-stimulated cells are principally T-lymphocytes. This is the first report on the decrease in PHA-stimulated proliferation ratio (stimulability) and RNA level in PBMC of DS patients in relation to age. q 2006 Clinical Cytometry Society

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“…However, cellular functions of C21ORF2 are still elusive. Studies on the genetic locus suggested that C21ORF2 might be associated with a series of human genetic diseases, such as Down syndrome (DS), which is caused by trisomy of chromosome 21 [2]. A reduction of C21ORF2 expression was observed in DS patients, and these patients were reported to be more sensitive to DNA damage [2,3], suggesting a possible association between C21ORF2 expression and the DNA damage response (DDR).…”

Section: Introductionmentioning

confidence: 99%

The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair

Xiao¹,

Han²,

Wang³

et al. 2015

ABBS

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Defective DNA damage response is a threat to genome stability and a proven cause of tumorigenesis. C21ORF2 (chromosome 21 open reading frame 2) is a novel gene on chromosome 21, and the C21ORF2 protein is found to interact with NEK1. Earlier studies showed that C21ORF2 might be associated with some human genetic diseases including Down syndrome. However, the cellular functions of C21ORF2 remain unknown. In the present study, we reported that C21ORF2 affected cell proliferation after DNA damage induced by ionizing radiation, and DNA repair was less efficient in C21ORF2-depleted cells compared with control cells. However, C21ORF2-knockdown cells did not show defects in the activation of the G2-phase DNA damage checkpoint. Furthermore, homologous recombination, but not non-homologous end joining repair, was found to be impaired after C21ORF2 attenuation, which could be rescued by the overexpression of NEK1, indicating that C21ORF2 functions in the same pathway as NEK1 in DNA damage repair.

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Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down Syndrome brain

Cited by 22 publications

References 36 publications

Flow cytometric comparison of RNA content in peripheral blood mononuclear cells of down syndrome patients and control individuals

Flow cytometric comparison of RNA content in peripheral blood mononuclear cells of down syndrome patients and control individuals

Age‐dependent decreases in mitogen‐stimulation level and RNA content in peripheral blood mononuclear cells of down syndrome patients

The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair

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