Recent insights into mechanisms preventing ectopic centromere formation

Dong, Qingyu; Yang, Jinpu; Gao, Jinxin; Li, Fēi

doi:10.1098/rsob.210189

Cited by 10 publications

(7 citation statements)

References 197 publications

(346 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over expression of CID during meiotic prophase resulted in ectopic localization to most of the chromatin, recruitment of kinetochore proteins like CENP-C and Spc105R, and sterility. Similar observations of ectopic localization have been made when CID is overexpressed in somatic cells [ 71 – 73 ]. Thus, it may be important to limit CID expression during prophase to avoid localization to non-centromeric locations.…”

Section: Discussionsupporting

confidence: 80%

A dynamic population of prophase CENP-C is required for meiotic chromosome segregation

Fellmeth,

Jang,

Persaud

et al. 2023

PLoS Genet

View full text Add to dashboard Cite

The centromere is an epigenetic mark that is a loading site for the kinetochore during meiosis and mitosis. This mark is characterized by the H3 variant CENP-A, known as CID in Drosophila. In Drosophila, CENP-C is critical for maintaining CID at the centromeres and directly recruits outer kinetochore proteins after nuclear envelope break down. These two functions, however, happen at different times in the cell cycle. Furthermore, in Drosophila and many other metazoan oocytes, centromere maintenance and kinetochore assembly are separated by an extended prophase. We have investigated the dynamics of function of CENP-C during the extended meiotic prophase of Drosophila oocytes and found that maintaining high levels of CENP-C for metaphase I requires expression during prophase. In contrast, CID is relatively stable and does not need to be expressed during prophase to remain at high levels in metaphase I of meiosis. Expression of CID during prophase can even be deleterious, causing ectopic localization to non-centromeric chromatin, abnormal meiosis and sterility. CENP-C prophase loading is required for multiple meiotic functions. In early meiotic prophase, CENP-C loading is required for sister centromere cohesion and centromere clustering. In late meiotic prophase, CENP-C loading is required to recruit kinetochore proteins. CENP-C is one of the few proteins identified in which expression during prophase is required for meiotic chromosome segregation. An implication of these results is that the failure to maintain recruitment of CENP-C during the extended prophase in oocytes would result in chromosome segregation errors in oocytes.

show abstract

Section: Discussionsupporting

confidence: 80%

A dynamic population of prophase CENP-C is required for meiotic chromosome segregation

Fellmeth,

Jang,

Persaud

et al. 2023

PLoS Genet

View full text Add to dashboard Cite

show abstract

“…CENPL is one of the proteins that constitute kinetosome, and overexpressed CENPL may affect the function of kinetochore. Previous studies have shown that kinetosome dysfunction might be a critical cause of chromosome instability and tumorigenesis [ 32 – 34 ]. Therefore, we hypothesize that overexpression of CENPL impairs the function of kinetosome and cause chromosomal instability, thereby causing or accelerating TP53 mutation in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CENPL mRNA potentially regulated by miR-340-3p predicts the prognosis of pancreatic cancer patients

Cui

Wang

et al. 2022

BMC Cancer

View full text Add to dashboard Cite

Background In our previous study it was found that CENPL was overexpressed in hepatocellular carcinoma and significantly predicted patient's prognosis. However, the expression and prognostic value of CENPL in other gastrointestinal tumors remain unknown. Therefore, we investigated the expression and prognostic value of CENPL in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). Methods In this study, Oncomine, GEPIA, OncoLnc, TIMER, cBioPortal, miRWalk and ENCORI databases were used to analyze the level of CENPL mRNA, prognostic value and potential regulatory mechanism of CENPL mRNA in tumors. The CENPL expression and clinicopathological data regarding PAAD were from the UCSC Xena database and univariate and multivariate Cox regression analyses were performed using R (Version 3.6.3). Immunohistochemical staining was used to verify the expression of CENPL protein in clinical specimens. Cytoscape (Version: 3.7.2) was used to visualize microRNA (miRNA) that potentially regulates CENPL. Results Gene differential expression analysis showed that CENPL mRNA was significantly overexpressed in ESCA, STAD, PAAD, COAD and READ (p < 0.01). The overexpression of CENPL mRNA was significantly correlated with the poor prognosis of PAAD patients (p < 0.05). However, there was no significant correlation between the level of CENPL mRNA and the prognosis of ESCA, STAD, COAD and READ patients (p > 0.05). Univariate and multivariate Cox regression analyses suggested that CENPL was a prognostic risk factor for PAAD. The mutation rate of CENPL in PAAD was 2.2% (17/850). There was no significant correlation between the CENPL expression and the infiltration levels of immune cells in PAAD (|Cor|< 0.5). Immunohistochemical staining showed that CENPL was overexpressed in 42% (11/26) of PAAD specimens, which was significantly higher compared with that in the normal tissues. The expression of miR-340-3p and miR-484 in PAAD were significantly lower than in the normal tissues (p < 0.05) and PAAD patients with lower expression of miR-340-3p had poorer prognosis (p < 0.05). Conclusion CENPL potentially regulated by miR-340-3p, is overexpressed in PAAD and predicts patient’s prognosis, suggestive of a diagnostic and prognostic value in PAAD patients.

show abstract

“…We speculate that there might be a possible reason for this phenomenon, which is the centromere loss of the fragment during cell culture of samples. The centromere is a chromosomal structure that is critical for the accurate segregation of genetic information during mitosis and meiosis [ 6 , 7 ]. It has been proven that the gain or loss of centromeres is important for genomic evolution and independent segregation of genes.…”

Section: Discussionmentioning

confidence: 99%

Prenatally detected six duplications at Xp22.33-p11.22: a case report

Zhang

et al. 2023

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

Background The discrepancy between the results of cytogenetics and the results of chromosome microarray analysis (CMA) has often led to confusion over genetic counselling for prenatal diagnosis. Case presentation The prenatal ultrasound results of a congenital heart defect (CHD) foetus displayed an apartial endocardial pad defect and permanently dilated coronary sinus and left superior vena cava at 21 weeks of gestation. Cytogenetic analysis, CMA, fluorescent in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) with foetal cord blood samples were used to detect the genetic aetiology. Routine G-binding cytogenetic analysis showed normal karyotypes in both the foetus’ and parents’ blood samples. CMA results demonstrated that there were 53.973-Mb recurrent CNVs at Xp22.33-p11.22, as confirmed by MLPA assay. Conclusions Herein, we described the CNV of six duplications at Xp22.33-p11.22 and the 53.973 Mb duplication CNV that was not found in foetal cord blood samples by conventional cytogenetic methods, and it was confirmed by CMA and MLPA. Our novel findings will provide helpful information for prenatal diagnosis and genetic counselling for foetal CHDs.

show abstract

Recent insights into mechanisms preventing ectopic centromere formation

Cited by 10 publications

References 197 publications

A dynamic population of prophase CENP-C is required for meiotic chromosome segregation

A dynamic population of prophase CENP-C is required for meiotic chromosome segregation

Overexpression of CENPL mRNA potentially regulated by miR-340-3p predicts the prognosis of pancreatic cancer patients

Prenatally detected six duplications at Xp22.33-p11.22: a case report

Contact Info

Product

Resources

About