scholarly journals Wounding Therapies for Prevention of Photocarcinogenesis

2022 ◽  
Vol 11 ◽  
Author(s):  
Timothy C. Frommeyer ◽  
Craig A. Rohan ◽  
Dan F. Spandau ◽  
Michael G. Kemp ◽  
Molly A. Wanner ◽  
...  
Keyword(s):  
Dermal Fibroblasts ◽  
Cell Cycle Checkpoint ◽  
Ultraviolet B ◽  
Treatment Modalities ◽  
Checkpoint Signaling ◽  
Non Melanoma Skin Cancer ◽  
Cycle Checkpoint ◽  
Chemical Peeling ◽  
Rising Incidence ◽  
Uvb Exposure

The occurrence of non-melanoma skin cancer (NMSC) is closely linked with advanced age and ultraviolet-B (UVB) exposure. More specifically, the development of NMSC is linked to diminished insulin-like growth factor-1 (IGF-1) signaling from senescent dermal fibroblasts in geriatric skin. Consequently, keratinocyte IGF-1 receptor (IGF-1R) remains inactive, resulting in failure to induce appropriate protective responses including DNA repair and cell cycle checkpoint signaling. This allows UVB-induced DNA damage to proliferate unchecked, which increases the likelihood of malignant transformation. NMSC is estimated to occur in 3.3 million individuals annually. The rising incidence results in increased morbidity and significant healthcare costs, which necessitate identification of effective treatment modalities. In this review, we highlight the pathogenesis of NMSC and discuss the potential of novel preventative therapies. In particular, wounding therapies such as dermabrasion, microneedling, chemical peeling, and fractionated laser resurfacing have been shown to restore IGF-1/IGF-1R signaling in geriatric skin and suppress the propagation of UVB-damaged keratinocytes. This wounding response effectively rejuvenates geriatric skin and decreases the incidence of age-associated NMSC.

scholarly journals Undamaged DNA Transmits and Enhances DNA Damage Checkpoint Signals in Early Embryos

2007 ◽  
Vol 27 (19) ◽  
pp. 6852-6862 ◽  
Author(s):  
Aimin Peng ◽  
Andrea L. Lewellyn ◽  
James L. Maller
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Nuclear Dna ◽  
Cell Cycle Checkpoint ◽  
Dna Damage Checkpoint ◽  
Checkpoint Signaling ◽  
Checkpoint Response ◽  
Egg Extracts ◽  
Cycle Checkpoint ◽  
Damaged Dna

ABSTRACT In Xenopus laevis embryos, the midblastula transition (MBT) at the 12th cell division marks initiation of critical developmental events, including zygotic transcription and the abrupt inclusion of gap phases into the cell cycle. Interestingly, although an ionizing radiation-induced checkpoint response is absent in pre-MBT embryos, introduction of a threshold amount of undamaged plasmid or sperm DNA allows a DNA damage checkpoint response to be activated. We show here that undamaged threshold DNA directly participates in checkpoint signaling, as judged by several dynamic changes, including H2AX phosphorylation, ATM phosphorylation and loading onto chromatin, and Chk1/Chk2 phosphorylation and release from nuclear DNA. These responses on physically separate threshold DNA require γ-H2AX and are triggered by an ATM-dependent soluble signal initiated by damaged DNA. The signal persists in egg extracts even after damaged DNA is removed from the system, indicating that the absence of damaged DNA is not sufficient to end the checkpoint response. The results identify a novel mechanism by which undamaged DNA enhances checkpoint signaling and provide an example of how the transition to cell cycle checkpoint activation during development is accomplished by maternally programmed increases in the DNA-to-cytoplasm ratio.

Cell cycle checkpoint signaling:

Toxicology ◽  
2002 ◽  
Vol 181-182 ◽  
pp. 475-481 ◽  
Author(s):  
J.A Pietenpol ◽  
Z.A Stewart
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Signaling ◽  
Cycle Checkpoint

scholarly journals Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death

2005 ◽  
Vol 4 (8) ◽  
pp. 1231-1238 ◽  
Author(s):  
Ragnhild V. Nome ◽  
Åse Bratland ◽  
Gunhild Harman ◽  
Øystein Fodstad ◽  
Yvonne Andersson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Histone Deacetylase ◽  
Cell Cycle Checkpoint ◽  
Histone Deacetylase Inhibition ◽  
Checkpoint Signaling ◽  
Cycle Checkpoint ◽  
Radiation Induced

scholarly journals Prevalent and Dynamic Binding of the Cell Cycle Checkpoint Kinase Rad53 to Gene Promoters

2021 ◽  
Author(s):  
Yi-Jun Sheu ◽  
Risa Karakida Kawaguchi ◽  
Jesse Gillis ◽  
Bruce Stillman
Keyword(s):  
Cell Cycle ◽  
Replication Initiation ◽  
Cell Cycle Checkpoint ◽  
Gene Promoters ◽  
Cellular Functions ◽  
Dynamic Binding ◽  
Checkpoint Kinase ◽  
Checkpoint Signaling ◽  
Genome Wide ◽  
Cycle Checkpoint

Replication of the genome must be coordinated with gene transcription and cellular metabolism. These processes are controlled in part by the Rad53 (CHEK2 in mammals) checkpoint kinase and the Mrc1 replisome component, especially following replication stress in the presence of limiting deoxyribonucleotides. We examined cell cycle regulated, genome-wide binding of Rad53 to chromatin. The kinase bound to sites of active DNA replication initiation and fork progression, but unexpectedly to the promoters of numerous genes (>20% of all genes) involved in many cellular functions. At some genes, Rad53 promoter binding correlated with changes in gene expression. Rad53 promoter binding to certain genes is influenced by sequence-specific transcription factors and less by checkpoint signaling. In checkpoint mutants, untimely activation of late-replicating origins reduces the transcription of nearby genes, with concomitant localization of Rad53 to their gene bodies. We suggest that the Rad53 checkpoint kinase coordinates genome-wide replication and transcription under stress conditions.

scholarly journals CtIP-dependent DNA resection is required for DNA damage checkpoint maintenance but not initiation

2012 ◽  
Vol 197 (7) ◽  
pp. 869-876 ◽  
Author(s):  
Arne Nedergaard Kousholt ◽  
Kasper Fugger ◽  
Saskia Hoffmann ◽  
Brian D. Larsen ◽  
Tobias Menzel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Dna Lesions ◽  
Cell Cycle Checkpoint ◽  
Dna Breaks ◽  
Checkpoint Signaling ◽  
Cycle Checkpoint ◽  
Dna End Resection ◽  
End Resection

To prevent accumulation of mutations, cells respond to DNA lesions by blocking cell cycle progression and initiating DNA repair. Homology-directed repair of DNA breaks requires CtIP-dependent resection of the DNA ends, which is thought to play a key role in activation of ATR (ataxia telangiectasia mutated and Rad3 related) and CHK1 kinases to induce the cell cycle checkpoint. In this paper, we show that CHK1 was rapidly and robustly activated before detectable end resection. Moreover, we show that the key resection factor CtIP was dispensable for initial ATR–CHK1 activation after DNA damage by camptothecin and ionizing radiation. In contrast, we find that DNA end resection was critically required for sustained ATR–CHK1 checkpoint signaling and for maintaining both the intra–S- and G2-phase checkpoints. Consequently, resection-deficient cells entered mitosis with persistent DNA damage. In conclusion, we have uncovered a temporal program of checkpoint activation, where CtIP-dependent DNA end resection is required for sustained checkpoint signaling.

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