Cell-cycle Checkpoints and Aneuploidy on the Path to Cancer

Wenzel, Elizabeth M.; Singh, Amareshwar T.K.

doi:10.21873/invivo.11197

Cited by 92 publications

(70 citation statements)

References 40 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As argued, impaired cohesin function can negatively impact on genome instability in at least three direct ways: by promoting aneuploidy due to unbalanced chromosome segregation, by favouring the formation of stalled fork--driven DNA breaks and by increasing the genotoxic impact of DNA lesions due to faulty repair. Importantly, both replication stress--related DNA damage and aneuploidy are regarded as drivers of the malignant transformation process (Bartkova et al 2005;Bartek and Lukas 2007;Wenzel and Singh 2018). The work here discussed provides a framework to understand how dynamic interfacing of cohesin with replication forks may influence both fork stability and the establishment of sister chromatid cohesion.…”

Section: Discussionmentioning

confidence: 97%

Cohesin dynamic association to chromatin and interfacing with replication forks in genome integrity maintenance

Villa-Hernández

Bermejo

2018

Curr Genet

View full text Add to dashboard Cite

Proliferating cells need to accurately duplicate and pass their genetic material on to daughter cells. Problems during replication and partition challenge the structural and numerical integrity of chromosomes. Diverse mechanisms, as the DNA replication checkpoint, survey the correct progression of replication and couple it with other cell cycle events to preserve genome integrity. The structural maintenance of chromosomes (SMC) cohesin complex primarily contributes to chromosome duplication by mediating the tethering of newly replicated sister chromatids, thus assisting their equal segregation in mitosis. In addition, cohesin exerts important functions in genome organization, gene expression and DNA repair. These are determined by cohesin's ability to bring together different DNA segments and, hence, by the fashion and dynamics of its interaction with chromatin. It recently emerged that cohesin contributes to the protection of stalled replication forks through a mechanism requiring its timely mobilization from unreplicated DNA and relocation to nascent strands. This mechanism relies on DNA replication checkpoint-dependent cohesin ubiquitylation and promotes nascent sister chromatid entrapment, likely contributing to preserve stalled replisome-fork architectural integrity. Here we review how cohesin dynamic association to chromatin is controlled through post-translational modifications to dictate its functions during chromosome duplication. We also discuss recent insights on the mechanism that mediates interfacing of replisome components with chromatin-bound cohesin and its contribution to the establishment of sister chromatid cohesion and the protection of stalled replication forks.

show abstract

Section: Discussionmentioning

confidence: 97%

Cohesin dynamic association to chromatin and interfacing with replication forks in genome integrity maintenance

Villa-Hernández

Bermejo

2018

Curr Genet

View full text Add to dashboard Cite

show abstract

“…Cell cycle is a highly regulated multipronged process orchestrated by a suite of cell-cycle regulators ( 158 ). Dysregulation of any of these regulatory mechanisms can result in genomic instability and polyploidy ( 159 ). EBNA2 was shown to specifically downregulate the mitotic arrest deficient 2 (MAD2) and upregulate Plk1, which can result in the activation of the anaphase promoting complex/cyclosome (APC/C) and subsequently securin degradation, thus engendering a metaphase-anaphase transition and opening the door toward polyploidy ( 45 ).…”

Section: Introductionmentioning

confidence: 99%

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Herbein

Nehme

2020

Front. Oncol.

View full text Add to dashboard Cite

Tumors are renowned as intricate systems that harbor heterogeneous cancer cells with distinctly diverse molecular signatures, sizes and genomic contents. Among those various genomic clonal populations within the complex tumoral architecture are the polyploid giant cancer cells (PGCC). Although described for over a century, PGCC are increasingly being recognized for their prominent role in tumorigenesis, metastasis, therapy resistance and tumor repopulation after therapy. A shared characteristic among all tumors triggered by oncoviruses is the presence of polyploidy. Those include Human Papillomaviruses (HPV), Epstein Barr Virus (EBV), Hepatitis B and C viruses (HBV and HCV, respectively), Human T-cell lymphotropic virus-1 (HTLV-1), Kaposi's sarcoma herpesvirus (KSHV) and Merkel polyomavirus (MCPyV). Distinct viral proteins, for instance Tax for HTLV-1 or HBx for HBV have demonstrated their etiologic role in favoring the appearance of PGCC. Different intriguing biological mechanisms employed by oncogenic viruses, in addition to viruses with high oncogenic potential such as human cytomegalovirus, could support the generation of PGCC, including induction of endoreplication, inactivation of tumor suppressors, development of hypoxia, activation of cellular senescence and others. Interestingly, chemoresistance and radioresistance have been reported in the context of oncovirus-induced cancers, for example KSHV and EBV-associated lymphomas and high-risk HPV-related cervical cancer. This points toward a potential linkage between the previously mentioned players and highlights PGCC as keystone cancer cells in virally-induced tumors. Subsequently, although new therapeutic approaches are actively needed to fight PGCC, attention should also be drawn to reveal the relationship between PGCC and oncoviruses, with the ultimate goal of establishing effective therapeutic platforms for treatment of virus-associated cancers. This review discusses the presence of PGCCs in tumors induced by oncoviruses, biological mechanisms potentially favoring their appearance, as well as their consequent implication at the clinical and therapeutic level.

show abstract

“…After mitosis, the cell itself divides and each daughter cell begins the cycle again from G1, or exits the cell cycle into G0. Progression from one stage to the next is controlled by the activities of kinase complexes made up of cyclins bound to cyclin-dependent kinases(Cdk) and cell cycle checkpoints are important control mechanisms that ensure the proper execution of cell cycle events [ 8 ]. When DNA damage response occurs, the G2/M checkpoint blocks the entry into mitosis to allow damage repair or direct cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Porcine reproductive and respiratory syndrome virus inhibits MARC-145 proliferation via inducing apoptosis and G2/M arrest by activation of Chk/Cdc25C and p53/p21 pathway

Song

Han

Jia

et al. 2018

Virol J

View full text Add to dashboard Cite

Porcine reproductive and respiratory syndrome virus(PRRSV) is an important immunosuppressive virus which can suppresses infected cells proliferation. In this work, we examined PRRSV ability to manipulate cell cycle progression of MARC-145 cells and explored the potential molecular mechanisms. The results showed that PRRSV infection imposed a growth-inhibitory effect on MARC-145 cells by inducing cell cycle arrest at G2/M phase. This arrest was due to the significant decrease of Cdc2-cyclinB1 complex activity in PRRSV-infected cells and the activity reduction was a result of Cdc2 Tyr15 phosphorylation and the accumulation of Cdc2 and cyclinB1 in the nucleus. Not only elevated Wee1 and Myt1 expression and inactivated Cdc25C, but also increase of p21 and 14–3-3σ in a p53-dependent manner caused the inhibitory Tyr15 phosphorylation of Cdc2. PRRSV infection also activated Chk1. Our data suggest PRRSV infection induces G2/M arrest via various molecular regulatory mechanisms. These results provide a new insights for PRRSV pathogenesis.

show abstract

Cell-cycle Checkpoints and Aneuploidy on the Path to Cancer

Cited by 92 publications

References 40 publications

Cohesin dynamic association to chromatin and interfacing with replication forks in genome integrity maintenance

Cohesin dynamic association to chromatin and interfacing with replication forks in genome integrity maintenance

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Porcine reproductive and respiratory syndrome virus inhibits MARC-145 proliferation via inducing apoptosis and G2/M arrest by activation of Chk/Cdc25C and p53/p21 pathway

Contact Info

Product

Resources

About