PDS5A and PDS5B in Cohesin Function and Human Disease

Zhang, Nenggang; Coutinho, Luiza E.; Pati, Debananda

doi:10.3390/ijms22115868

Cited by 24 publications

(16 citation statements)

References 187 publications

(328 reference statements)

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“…PDS5A, a sister chromatid cohesion protein PDS homolog A, is responsible for unloading auxin from chromatin, while CDCA5 (sororin) is involved in establishing sister chromatid cohesion (SCC) ( 15 ). Alterations in PDS5A expression levels have been observed in breast, kidney, esophagus, stomach, liver and colon cancer ( 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of CDCA5 suppresses malignant progression of breast cancer cells by regulating PDS5A

et al. 2022

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Breast cancer is one of the most common malignant tumors in women. Cell division cycle-associated 5 (CDCA5) is closely associated with the behavior of various cancer types. The aim of the present study was to explore the effect of CDCA5 on breast cancer. Western blot analysis and reverse transcription-quantitative PCR were used to detect the expression level of CDCA5 in human normal mammary cells and human breast cancer cell lines. To determine its function in MDA-MB-231 cells, CDCA5 was silenced in MDA-MB-231 cells by transient short hairpin RNA transfection. Cell Counting Kit-8 and clonogenicity assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to detect cell invasion and migration. Western blot analysis was used to detect the protein expressions of Ki67 and PCNA associated with proliferation, MMP2 and MMP9 associated with migration. CDCA5 was found to be markedly increased in breast cancer cell lines. CDCA5 knockdown was able to suppress cell proliferation, invasion and migration. CDCA5 inhibition downregulated PDS5 cohesin-associated factor A (PDS5A) expression in breast cancer cells. PDS5A overexpression was found to reverse the effect of CDCA5 inhibition on breast cancer cell proliferation and migration. CDCA5 knockdown was shown to suppress the malignant progression of breast cancer cells by regulating PDS5A. The present findings may provide new potential targets for breast cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Knockdown of CDCA5 suppresses malignant progression of breast cancer cells by regulating PDS5A

et al. 2022

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“…STAG2 is the most frequently mutated in solid cancers [ 219 , 220 ], and in hematologic malignancies, genes including STAG1 , STAG2 , RAD21 , SMC1A , and SMC3 are frequently mutated [ 221 – 223 ]. Also, precocious dissociation of sisters 5 (PDS5) is an associated protein of cohesin complex [ 224 ]. It has been shown that PDS5B protein behaves as a tumour suppressor, as PDS5B gene expression level is reduced in gastric and colorectal cancers [ 225 ], and about 47% of breast cancer have low expression of PDS5B [ 226 ].…”

Section: Key Structural Elements Mediating 3d Chromatin Interactionsmentioning

confidence: 99%

3D chromatin architecture and transcription regulation in cancer

2022

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Chromatin has distinct three-dimensional (3D) architectures important in key biological processes, such as cell cycle, replication, differentiation, and transcription regulation. In turn, aberrant 3D structures play a vital role in developing abnormalities and diseases such as cancer. This review discusses key 3D chromatin structures (topologically associating domain, lamina-associated domain, and enhancer–promoter interactions) and corresponding structural protein elements mediating 3D chromatin interactions [CCCTC-binding factor, polycomb group protein, cohesin, and Brother of the Regulator of Imprinted Sites (BORIS) protein] with a highlight of their associations with cancer. We also summarise the recent development of technologies and bioinformatics approaches to study the 3D chromatin interactions in gene expression regulation, including crosslinking and proximity ligation methods in the bulk cell population (ChIA-PET and HiChIP) or single-molecule resolution (ChIA-drop), and methods other than proximity ligation, such as GAM, SPRITE, and super-resolution microscopy techniques.

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“…Apart from its four core structural subunits, the cohesin complex also contains several accessory and regulatory subunits, including PDS5, WAPL, sororin, and the loading-complex-forming proteins, NIPBL and MAU2. In vertebrates, PDS5 (there are two isoforms: PDS5A and PDS5B) is essential for the dissociation of cohesin complexes from the chromosome arms in early mitosis [ 71 , 72 ]. Another cohesin cofactor subunit, called WAPL, associates with PDS5 and, similarly to PDS5, acts as a crucial protagonist in the removal of cohesin complexes during the prophase [ 73 , 74 ].…”

Section: The Cohesin Complex and Its Role In Chromosome Segregationmentioning

confidence: 99%

“…The removal of cohesin from chromosomes occurs in a two-step manner. Most cohesin complexes dissociate from the chromosome arms by a separase-independent pathway during prophase [ 89 ] which requires the activity of the kinases Aurora B and PLK1, as well as the cohesin subunit proteins WAPL and PDS5 [ 72 ]. Furthermore, the phosphorylation of sororin during mitosis causes its inability to antagonize WAPL binding to PDS5, which results in the association of WAPL with PDS5 and the subsequent removal of cohesin complexes from the arms of chromosomes [ 88 ].…”

Section: The Cohesin Complex and Its Role In Chromosome Segregationmentioning

confidence: 99%

The Interplay of Cohesin and RNA Processing Factors: The Impact of Their Alterations on Genome Stability

Osadska

Selicky

Kretova

et al. 2022

IJMS

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Cohesin, a multi-subunit protein complex, plays important roles in sister chromatid cohesion, DNA replication, chromatin organization, gene expression, transcription regulation, and the recombination or repair of DNA damage. Recently, several studies suggested that the functions of cohesin rely not only on cohesin-related protein–protein interactions, their post-translational modifications or specific DNA modifications, but that some RNA processing factors also play an important role in the regulation of cohesin functions. Therefore, the mutations and changes in the expression of cohesin subunits or alterations in the interactions between cohesin and RNA processing factors have been shown to have an impact on cohesion, the fidelity of chromosome segregation and, ultimately, on genome stability. In this review, we provide an overview of the cohesin complex and its role in chromosome segregation, highlight the causes and consequences of mutations and changes in the expression of cohesin subunits, and discuss the RNA processing factors that participate in the regulation of the processes involved in chromosome segregation. Overall, an understanding of the molecular determinants of the interplay between cohesin and RNA processing factors might help us to better understand the molecular mechanisms ensuring the integrity of the genome.

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PDS5A and PDS5B in Cohesin Function and Human Disease

Cited by 24 publications

References 187 publications

Knockdown of CDCA5 suppresses malignant progression of breast cancer cells by regulating PDS5A

Knockdown of CDCA5 suppresses malignant progression of breast cancer cells by regulating PDS5A

3D chromatin architecture and transcription regulation in cancer

The Interplay of Cohesin and RNA Processing Factors: The Impact of Their Alterations on Genome Stability

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