scholarly journals Kinetics of the UV-induced DNA damage response in relation to cell cycle phase. Correlation with DNA replication

2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Hong Zhao ◽  
Frank Traganos ◽  
Zbigniew Darzynkiewicz
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Cell Cycle Phase ◽  
Phase Correlation ◽  
Cycle Phase ◽  
Damage Response ◽  
Kinetics Of

scholarly journals Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

2021 ◽  
Author(s):  
Swathy Babu ◽  
Yuki Takeuchi ◽  
Ichiro Masai
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Damage Response ◽  
Dna Damage Responses

Btg3-associated nuclear protein (Banp) was originally identified as a nuclear matrix-associated protein and it functions as a tumor suppressor. At molecular level, Banp regulates transcription of metabolic genes via a CGCG-containing motif called the Banp motif. However, its physiological roles in embryonic development are unknown. Here we report that Banp is indispensable for DNA damage response and chromosome segregation during mitosis. Zebrafish banp mutants show mitotic arrest and apoptosis in developing retina. We found that DNA replication stress and tp53-dependent DNA damage responses were activated to induce apoptosis in banp mutants, suggesting that Banp is required for integrity of DNA replication and DNA damage repair. Furthermore, in banp mutants, chromosome segregation was not smoothly processed from prometaphase to anaphase, leading to a prolonged M-phase. Our RNA- and ATAC-sequencing identified 31 candidates for direct Banp target genes that carry the Banp motif. Interestingly, two chromosome segregation regulators, cenpt and ncapg, are included in this list. Thus, Banp directly regulates transcription of cenpt and ncapg to promote chromosome segregation during mitosis. Our findings provide the first in vivo evidence that Banp is required for cell-cycle progression and cell survival by regulating DNA damage responses and chromosome segregation during mitosis.

scholarly journals Lack of CCAAT Enhancer Binding Protein Beta (C/EBPβ) in Uterine Epithelial Cells Impairs Estrogen-Induced DNA Replication, Induces DNA Damage Response Pathways, and Promotes Apoptosis

2010 ◽  
Vol 30 (7) ◽  
pp. 1607-1619 ◽  
Author(s):  
Cyril Ramathal ◽  
Indrani C. Bagchi ◽  
Milan K. Bagchi
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
S Phase ◽  
Uterine Epithelial Cells ◽  
Cycle Arrest ◽  
Damage Response

ABSTRACT Female mice lacking the transcription factor C/EBPβ are infertile and display markedly reduced estrogen (E)-induced proliferation of the uterine epithelial lining during the reproductive cycle. The present study showed that E-stimulated luminal epithelial cells of a C/EBPβ-null uterus are able to proceed through the G1 phase of the cell cycle before getting arrested in the S phase. This cell cycle arrest was accompanied by markedly reduced levels of expression of E2F3, an E2F family member, and a lack of nuclear localization of cyclin E, a critical regulator of cdk2. An increased nuclear accumulation of p27, an inhibitor of the cyclin E-cdk2 complex, was also observed for the mutant epithelium. Gene expression profiling of C/EBPβ-null uterine epithelial cells revealed that the blockade of E-induced DNA replication triggers the activation of several well-known components of the DNA damage response pathway, such as ATM, ATR, histone H2AX, checkpoint kinase 1, and tumor suppressor p53. The activation of p53 by ATM/ATR kinase led to increased levels of expression of p21, an inhibitor of G1-S-phase progression, which helps maintain cell cycle arrest. Additionally, p53-dependent mechanisms contributed to an increased apoptosis of replication-defective cells in the C/EBPβ-null epithelium. C/EBPβ, therefore, is an essential mediator of E-induced growth and survival of uterine epithelial cells of cycling mice.

scholarly journals Gene co-expression analysis of human RNASEH2A reveals functional networks associated with DNA replication, DNA damage response, and cell cycle regulation

2020 ◽  
Author(s):  
Stefania Marsili ◽  
Ailone Tichon ◽  
Francesca Storici
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Cell Cycle Regulation ◽  
Functional Networks ◽  
Biological Processes ◽  
Damage Response ◽  
Rnase H2 ◽  
Cycle Regulation

AbstractRibonuclease H2 (RNase H2) is a key enzyme for the removal of RNA found in DNA-RNA hybrids, playing a fundamental role in biological processes such as DNA replication, telomere maintenance and DNA damage repair. RNase H2 is a trimer composed of three subunits, being RNASEH2A the catalytic subunit. RNASEH2A expression levels have been shown to be upregulated in transformed and cancer cells. In this study we used a bioinformatics approach to identify RNASEH2A co-expressed genes in different human tissues to uncover biological processes in which RNASEH2A is involved. By implementing this approach, we identified functional networks for RNASEH2A that are not only involved in the processes of DNA replication and DNA damage response, but also in cell cycle regulation. Additional examination of protein-protein networks for RNASEH2A by the STRING database analysis, revealed a high co-expression correlation between RNASEH2A and the genes of the protein networks identified. Mass spectrometry analysis of RNASEH2A-bound proteins highlighted players functioning in cell cycle regulation. Further bioinformatics investigation showed increased gene expression of RNASEH2A in different types of actively cycling cells and tissues, and particularly in several cancers, supporting a biological role for RNASEH2A, but not the other two subunits of RNase H2, in cell proliferation.

scholarly journals Role of the Polymerase ϵ sub-unit DPB2 in DNA replication, cell cycle regulation and DNA damage response in Arabidopsis

2016 ◽  
pp. gkw449 ◽  
Author(s):  
José Antonio Pedroza-Garcia ◽  
Séverine Domenichini ◽  
Christelle Mazubert ◽  
Mickael Bourge ◽  
Charles White ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Cell Cycle Regulation ◽  
Damage Response ◽  
Cycle Regulation

scholarly journals LINE-1 expression in cancer correlates with DNA damage response, copy number variation, and cell cycle progression

2020 ◽  
Author(s):  
Wilson McKerrow ◽  
Xuya Wang ◽  
Paolo Mita ◽  
Song Cao ◽  
Mark Grivainis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Copy Number Variation ◽  
Dna Damage Response ◽  
Copy Number ◽  
Host Cells ◽  
Cycle Progression ◽  
Damage Response ◽  
Number Variation

ABSTRACTRetrotransposons are genomic DNA sequences that are capable of copying themselves to new genomic locations via RNA intermediates; LINE-1 is the only retrotransposon that remains autonomous and active in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues, but LINE-1 is active in many cancers. Recent studies using LINE-1 constructs indicate that host cells activate a DNA damage response (DDR) to repair retrotransposition intermediates and resolve conflicts between LINE-1 and DNA replication. Using multi-omic data from the CPTAC project, we found correlations between LINE-1 expression and ATM-MRN-SMC DDR signalling in endometrial cancer and between LINE-1 and the ATR-CHEK1 pathway in p53 wild type breast cancer. This provides evidence that conflicts between LINE-1 and DNA replication occur in at least some human cancers. Furthermore, LINE-1 expression in these cancers is correlated with the total amount of copy number variation genome wide, indicating that, when active in cancer, pointing to a direct impact of LINE-1 associated DNA damage on genome structure. We also find that, in endometrial and ovarian cancer, LINE-1 expression is correlated with the expression of genes that drive cycle progression including E2F3, PLK1 and Aurora kinase B. This study provides evidence, supporting recent work in model cell lines, of a LINE-1/DDR connection in human tumors and raises the possibility of additional interactions between LINE-1 and the cell cycle.

scholarly journals Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Wei Zou ◽  
Zekun Wang ◽  
Min Xiong ◽  
Aaron Yun Chen ◽  
Peng Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Parvovirus B19 ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Cycle Arrest ◽  
Damage Response ◽  
Cellular Dna

ABSTRACTHuman parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication.IMPORTANCEHuman parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly associated with the replicating single-stranded DNA viral genome and played a critical role in viral DNA replication. In contrast, the DNA damage response-induced phosphorylated forms of RPA32 were dispensable for viral DNA replication.

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