scholarly journals BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution

2006 ◽  
Vol 34 (5) ◽  
pp. 1416-1426 ◽  
Author(s):  
C.-X. Deng
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Genetic Instability ◽  
Cell Cycle Checkpoint ◽  
Cancer Evolution ◽  
Damage Response ◽  
Cycle Checkpoint

Molecular characterization of collaborator of ARF (CARF) as a DNA damage response and cell cycle checkpoint regulatory protein

2014 ◽  
Vol 322 (2) ◽  
pp. 324-334 ◽  
Author(s):  
Rumani Singh ◽  
Rajkumar S. Kalra ◽  
Kamrul Hasan ◽  
Zeenia Kaul ◽  
Caroline T. Cheung ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Molecular Characterization ◽  
Dna Damage Response ◽  
Regulatory Protein ◽  
Cell Cycle Checkpoint ◽  
Damage Response ◽  
Cycle Checkpoint

scholarly journals Intersection of Two Checkpoints: Could Inhibiting the DNA Damage Response Checkpoint Rescue Immune Checkpoint-Refractory Cancer?

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3415
Author(s):  
Peter H. Goff ◽  
Rashmi Bhakuni ◽  
Thomas Pulliam ◽  
Jung Hyun Lee ◽  
Evan T. Hall ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Tumor Immunity ◽  
Immune Checkpoint ◽  
Ataxia Telangiectasia ◽  
Management Strategies ◽  
Adaptive Immune Response ◽  
Cell Cycle Checkpoint ◽  
Damage Response ◽  
Cycle Checkpoint

Metastatic cancers resistant to immunotherapy require novel management strategies. DNA damage response (DDR) proteins, including ATR (ataxia telangiectasia and Rad3-related), ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase), have been promising therapeutic targets for decades. Specific, potent DDR inhibitors (DDRi) recently entered clinical trials. Surprisingly, preclinical studies have now indicated that DDRi may stimulate anti-tumor immunity to augment immunotherapy. The mechanisms governing how DDRi could promote anti-tumor immunity are not well understood; however, early evidence suggests that they can potentiate immunogenic cell death to recruit and activate antigen-presenting cells to prime an adaptive immune response. Merkel cell carcinoma (MCC) is well suited to test these concepts. It is inherently immunogenic as ~50% of patients with advanced MCC persistently benefit from immunotherapy, making MCC one of the most responsive solid tumors. As is typical of neuroendocrine cancers, dysfunction of p53 and Rb with upregulation of Myc leads to the very rapid growth of MCC. This suggests high replication stress and susceptibility to DDRi and DNA-damaging agents. Indeed, MCC tumors are particularly radiosensitive. Given its inherent immunogenicity, cell cycle checkpoint deficiencies and sensitivity to DNA damage, MCC may be ideal for testing whether targeting the intersection of the DDR checkpoint and the immune checkpoint could help patients with immunotherapy-refractory cancers.

scholarly journals Arabidopsis Casein Kinase 2 triggers Stem Cell Exhaustion under Al Toxicity and Phosphate Deficiency Through activation of the DNA Damage Response pathway

2020 ◽  
Author(s):  
Wei Pengliang ◽  
Manon Demulder ◽  
Pascale David ◽  
Thomas Eekhout ◽  
Kaoru Okamoto Yoshiyama ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Dna Damage Response ◽  
Stem Cell Niche ◽  
Al Toxicity ◽  
Cell Cycle Checkpoint ◽  
Damage Response ◽  
Cycle Checkpoint ◽  
Cell Niche ◽  
Dna Damage Response Pathway

Aluminum (Al) toxicity and inorganic phosphate (Pi) limitation are widespread chronic abiotic and mutually enhancing stresses that profoundly affect crop yield. Both stresses cause a strong inhibition of root growth, resulting from a progressive exhaustion of the stem cell niche. Here, we report on a casein kinase 2 (CK2) inhibitor identified by its capability to maintain a functional root stem cell niche under Al toxic conditions. CK2 operates through phosphorylation of the cell cycle checkpoint activator SUPPRESSOR OF GAMMA RADIATION1 (SOG1), priming its activity under DNA-damaging conditions. In addition to yielding Al tolerance, CK2 and SOG1 inactivation prevents meristem exhaustion under Pi starvation, revealing the existence of a low Pi-induced cell cycle checkpoint that depends on the DNA damage activator ATAXIA-TELANGIECTASIA MUTATED. Overall, our data reveal an important physiological role for the plant DNA damage response pathway under agriculturally limiting growth conditions, opening new avenues to cope with Pi limitation.

An intimate alliance of DNA-damage response network with cell-cycle checkpoints amid events of uncontrolled cellular proliferation- a minireview

2020 ◽  
Vol 20 ◽  
Author(s):  
Aroni Chatterjee ◽  
Keshav Rajarshi ◽  
Rajni Khan ◽  
Hiya Ghosh ◽  
Sonia Kapoor ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Cellular Proliferation ◽  
Cell Senescence ◽  
Cell Cycle Checkpoint ◽  
Effector Proteins ◽  
Cell Cycle Checkpoints ◽  
Response Network ◽  
Damage Response

: There is close interdependence between cell survival, cell senescence, events of the cell cycle, apoptosis, malignancy development, and tumor responses to cancer treatment. Intensive studies and elaborate researches have been conducted on the functional aspects of oncogenes, tumor suppressor genes, apoptotic genes, and members guiding cell cycle regulation. These disquisitions have put forward the existence of a highly organized response pathway termed as a DNAdamage response network. The pathways detecting DNA damage and signaling are intensively linked to the events of cellcycle arrest, cell proliferation, apoptosis, and cell senescence. DNA damage responses are complex systems that incorporate specific "sensor" and "transducer" proteins, for assessment of damage and signal transmission, respectively. These signals are thereafter relayed upon various "effector" proteins involved in different cellular pathways. It may include those governing cell-cycle checkpoints, participating in DNA repair, cell senescence, and apoptosis. This review discusses about the role of tumour suppressor gene, oncogenes, cell cycle checkpoint regulators during DNA damage response and regulation.

scholarly journals Deciphering the Genetic Aberrations in DNA Damage Response Genes and Their Possible Association with HNSCC

2020 ◽  
pp. 156-169
Author(s):  
L. Akshayaa ◽  
A. S. Smiline Girija ◽  
A. Paramasivam ◽  
J. Vijayashree Priyadharsini
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Wide Spectrum ◽  
Survival Curve ◽  
Cell Cycle Checkpoint ◽  
Single Nucleotide Variants ◽  
Differential Expression Pattern ◽  
Damage Response ◽  
Cycle Checkpoint ◽  
High Level

Head and neck squamous cell carcinoma (HNSCC) includes carcinomas in the oral cavity, pharynx and larynx. It is considered as the sixth most common form of cancer in the world. Several studies have confirmed that smoking and alcohol consumption are the major risk factors for HNSCC. DNA damage response genes play an important role in the maintenance of the genome. Defects in cell cycle checkpoint and DNA repair mechanisms, such as mutation or abnormalities, may lead to the wide spectrum of human diseases. The present study employs databases and computational tools to identify the genetic abnormalities associated with DNA damage related genes which might have a direct or indirect association with HNSCC. The demographic details of HNSCC patients was obtained from The Cancer Gene Atlas (TCGA, Firehose Legacy) dataset hosted by the cBioportal database. The oncoprint data analysis revealed the highest frequency of gene alteration in the ATR gene (15%), followed by ATM, BRCA2 and CHEK2 (5%). Other genes showed less than 5% alteration. The gene expression profile of ATR gene revealed its differential expression pattern in different grades of tumor relative to normal samples. The survival curve analysis using Kaplan-Meier method revealed that a high level expression of the ATR gene leads to poor survival rate in the female HNSCC patients when compared to males. Thus the present study has identified gross and single nucleotide variants in the ATR gene which could have a putative role in the development of tumor. Further experimental research is required to confirm this association.

scholarly journals Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response

2003 ◽  
Vol 160 (7) ◽  
pp. 1017-1027 ◽  
Author(s):  
Gary D. Kao ◽  
W. Gillies McKenna ◽  
Matthew G. Guenther ◽  
Ruth J. Muschel ◽  
Mitchell A. Lazar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Dna Damage Response ◽  
Lethal Dose ◽  
Cell Cycle Checkpoint ◽  
Dna Breaks ◽  
Damage Response ◽  
Cycle Checkpoint ◽  
Histone Deacetylase 4

Anumber of proteins are recruited to nuclear foci upon exposure to double-strand DNA damage, including 53BP1 and Rad51, but the precise role of these DNA damage–induced foci remain unclear. Here we show in a variety of human cell lines that histone deacetylase (HDAC) 4 is recruited to foci with kinetics similar to, and colocalizes with, 53BP1 after exposure to agents causing double-stranded DNA breaks. HDAC4 foci gradually disappeared in repair-proficient cells but persisted in repair-deficient cell lines or cells irradiated with a lethal dose, suggesting that resolution of HDAC4 foci is linked to repair. Silencing of HDAC4 via RNA interference surprisingly also decreased levels of 53BP1 protein, abrogated the DNA damage–induced G2 delay, and radiosensitized HeLa cells. Our combined results suggest that HDAC4 is a critical component of the DNA damage response pathway that acts through 53BP1 and perhaps contributes in maintaining the G2 cell cycle checkpoint.

scholarly journals CHD4 in the DNA-damage response and cell cycle progression: not so NuRDy now

2013 ◽  
Vol 41 (3) ◽  
pp. 777-782 ◽  
Author(s):  
Aoife O’Shaughnessy ◽  
Brian Hendrich
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Transcriptional Regulation ◽  
Dna Damage Response ◽  
Cell Cycle Progression ◽  
Cell Cycle Checkpoint ◽  
Loss Of Function ◽  
Nurd Complex ◽  
Cycle Progression ◽  
Damage Response

The CHD4 (chromodomain-helicase-DNA-binding 4) (or Mi-2β) protein is a founding component of the NuRD (nucleosome remodelling and deacetylation) complex. NuRD has long been known to function in transcriptional regulation, and is conserved throughout the animal and plant kingdoms. In recent years, evidence has steadily accumulated indicating that CHD4 can both function outside of the NuRD complex and also play important roles in cellular processes other than transcriptional regulation. A number of loss-of-function studies have identified important roles for CHD4 in the DNA-damage response and in cell cycle progression through S-phase and into G2. Furthermore, as part of NuRD, it participates in regulating acetylation levels of p53, thereby indirectly regulating the G1/S cell cycle checkpoint. Although CHD4 has a somewhat complicated relationship with the cell cycle, recent evidence indicates that CHD4 may exert some tumour-suppressor functions in human carcinogenesis. CHD4 is a defining member of the NuRD complex, but evidence is accumulating that CHD4 also plays important NuRD-independent roles in the DNA-damage response and cell cycle progression, as well as in transcriptional regulation.

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