scholarly journals Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis

2017 ◽  
Vol 8 (3) ◽  
pp. e2664-e2664 ◽  
Author(s):  
Jayesh Deshmukh ◽  
Ruth Pofahl ◽  
Ingo Haase
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Uv Light ◽  
Skin Carcinogenesis ◽  
Damage Response

scholarly journals DNA Damage Response in the Adaptive Arm of the Immune System: Implications for Autoimmunity

2021 ◽  
Vol 22 (11) ◽  
pp. 5842
Author(s):  
Theodora Manolakou ◽  
Panayotis Verginis ◽  
Dimitrios T. Boumpas
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Immune Cells ◽  
Uv Light ◽  
Adaptive Immune ◽  
Physiological Processes ◽  
Adaptive Immune Cells ◽  
Damage Response ◽  
Environmental Agents ◽  
Dna Alterations

In complex environments, cells have developed molecular responses to confront threats against the genome and achieve the maintenance of genomic stability assuring the transfer of undamaged DNA to their progeny. DNA damage response (DDR) mechanisms may be activated upon genotoxic or environmental agents, such as cytotoxic drugs or ultraviolet (UV) light, and during physiological processes requiring DNA transactions, to restore DNA alterations that may cause cellular malfunction and affect viability. In addition to the DDR, multicellular organisms have evolved specialized immune cells to respond and defend against infections. Both adaptive and innate immune cells are subjected to DDR processes, either as a prerequisite to the immune response, or as a result of random endogenous and exogenous insults. Aberrant DDR activities have been extensively studied in the immune cells of the innate arm, but not in adaptive immune cells. Here, we discuss how the aberrant DDR may lead to autoimmunity, with emphasis on the adaptive immune cells and the potential of therapeutic targeting.

scholarly journals FLYWCH1, a Multi-Functional Zinc Finger Protein Contributes to the DNA Repair Pathway

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 889
Author(s):  
Sheema Almozyan ◽  
James Coulton ◽  
Roya Babaei-Jadidi ◽  
Abdolrahman S. Nateri
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Zinc Finger ◽  
Dna Damage Response ◽  
Zinc Finger Protein ◽  
Uv Light ◽  
Potential Contribution ◽  
Dna Damage And Repair ◽  
Endogenous Expression ◽  
Damage Response

Over recent years, several Cys2-His2 (C2H2) domain-containing proteins have emerged as critical players in repairing DNA-double strand breaks. Human FLYWCH1 is a newly characterised nuclear transcription factor with (C2H2)-type zinc-finger DNA-binding domains. Yet, our knowledge about FLYWCH1 is still in its infancy. This study explores the expression, role and regulation of FLYWCH1 in the context of DNA damage and repair. We provide evidence suggesting a potential contribution of FLYWCH1 in facilitating the recruitment of DNA-damage response proteins (DDRPs). We found that FLYWCH1 colocalises with γH2AX in normal fibroblasts and colorectal cancer (CRC) cell lines. Importantly, our results showed that enforced expression of FLYWCH1 induces the expression of γH2AX, ATM and P53 proteins. Using an ATM-knockout (ATMKO) model, we indicated that FLYWCH1 mediates the phosphorylation of H2AX (Ser139) independently to ATM expression. On the other hand, the induction of DNA damage using UV-light induces the endogenous expression of FLYWCH1. Conversely, cisplatin treatment reduces the endogenous level of FLYWCH1 in CRC cell lines. Together, our findings uncover a novel FLYWCH1/H2AX phosphorylation axis in steady-state conditions and during the induction of the DNA-damage response (DDR). Although the role of FLYWCH1 within the DDR machinery remains largely uncharacterised and poorly understood, we here report for the first-time findings that implicate FLYWCH1 as a potential participant in the DNA damage response signaling pathways.

scholarly journals CUL4A Abrogation Augments DNA Damage Response and Protection against Skin Carcinogenesis

2009 ◽  
Vol 34 (4) ◽  
pp. 451-460 ◽  
Author(s):  
Liren Liu ◽  
Sharrell Lee ◽  
Jianxuan Zhang ◽  
Sara B. Peters ◽  
Jeffrey Hannah ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Skin Carcinogenesis ◽  
Damage Response

scholarly journals Characterization of mec1Kinase-Deficient Mutants and of New Hypomorphic mec1Alleles Impairing Subsets of the DNA Damage Response Pathway

2001 ◽  
Vol 21 (12) ◽  
pp. 3913-3925 ◽  
Author(s):  
Vera Paciotti ◽  
Michela Clerici ◽  
Maddalena Scotti ◽  
Giovanna Lucchini ◽  
Maria Pia Longhese
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Cell Cycle Progression ◽  
Uv Light ◽  
Protein A ◽  
S Phase ◽  
Specific Cell ◽  
Dna Damage Checkpoints ◽  
Damage Response

ABSTRACT DNA damage checkpoints lead to the inhibition of cell cycle progression following DNA damage. The Saccharomyces cerevisiae Mec1 checkpoint protein, a phosphatidylinositol kinase-related protein, is required for transient cell cycle arrest in response to DNA damage or DNA replication defects. We show thatmec1 kinase-deficient (mec1kd) mutants are indistinguishable from mec1Δ cells, indicating that the Mec1 conserved kinase domain is required for all known Mec1 functions, including cell viability and proper DNA damage response. Mec1kd variants maintain the ability to physically interact with both Ddc2 and wild-type Mec1 and cause dominant checkpoint defects when overproduced in MEC1 cells, impairing the ability of cells to slow down S phase entry and progression after DNA damage in G1 or during S phase. Conversely, an excess of Mec1kd inMEC1 cells does not abrogate the G2/M checkpoint, suggesting that Mec1 functions required for response to aberrant DNA structures during specific cell cycle stages can be separable. In agreement with this hypothesis, we describe two new hypomorphic mec1 mutants that are completely defective in the G1/S and intra-S DNA damage checkpoints but properly delay nuclear division after UV irradiation in G2. The finding that these mutants, although indistinguishable frommec1Δ cells with respect to the ability to replicate a damaged DNA template, do not lose viability after UV light and methyl methanesulfonate treatment suggests that checkpoint impairments do not necessarily result in hypersensitivity to DNA-damaging agents.

2118-P: Regulation of Ataxia-Telangiectasia and Rad3-Related (ATR)–Dependent DNA Damage Response by Nitric Oxide in ß-Cells

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2118-P
Author(s):  
CHAY TENG YEO ◽  
BRYNDON OLESON ◽  
JOHN A. CORBETT ◽  
JAMIE K. SCHNUCK
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Damage Response
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