DNA interstrand crosslinks: Repair, cell signaling, and therapeutic implications

2010 ◽  
pp. n/a-n/a
Author(s):  
Karen M. Vasquez ◽  
Randy J. Legerski
Keyword(s):  
Cell Signaling ◽  
Therapeutic Implications ◽  
Interstrand Crosslinks ◽  
Dna Interstrand Crosslinks

scholarly journals trans-Fatty acids promote p53-dependent apoptosis triggered by cisplatin-induced DNA interstrand crosslinks via the Nox-RIP1-ASK1-MAPK pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yusuke Hirata ◽  
Miki Takahashi ◽  
Yuto Yamada ◽  
Ryosuke Matsui ◽  
Aya Inoue ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mapk Pathway ◽  
Regulatory Protein ◽  
Strand Break ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Apoptotic Pathway ◽  
Interstrand Crosslinks ◽  
Pathway Activation ◽  
Dna Interstrand Crosslinks

Abstracttrans-Fatty acids (TFAs) are food-derived fatty acids associated with various diseases including cardiovascular diseases. However, the underlying etiology is poorly understood. Here, we show a pro-apoptotic mechanism of TFAs such as elaidic acid (EA), in response to DNA interstrand crosslinks (ICLs) induced by cisplatin (CDDP). We previously reported that TFAs promote apoptosis induced by doxorubicin (Dox), a double strand break (DSB)-inducing agent, via a non-canonical apoptotic pathway independent of tumor suppressor p53 and apoptosis signal-regulating kinase (ASK1), a reactive oxygen species (ROS)-responsive kinase. However, here we found that in the case of CDDP-induced apoptosis, EA-mediated pro-apoptotic action was reversed by knockout of either p53 or ASK1, despite no increase in p53 apoptotic activity. Upon CDDP treatment, EA predominantly enhanced ROS generation, ASK1-p38/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathway activation, and ultimately cell death, all of which were suppressed either by co-treatment of the NADPH oxidase (Nox) inhibitor Apocynin, or by knocking out its regulatory protein, receptor-interacting protein 1 (RIP1). These results demonstrate that in response to CDDP ICLs, TFAs promote p53-dependent apoptosis through the enhancement of the Nox-RIP1-ASK1-MAPK pathway activation, providing insight into the diverse pathogenetic mechanisms of TFAs according to the types of DNA damage.

scholarly journals Differential functions of FANCI and FANCD2 ubiquitination stabilize ID2 complex on DNA

2020 ◽  
Author(s):  
Martin L. Rennie ◽  
Kimon Lemonidis ◽  
Connor Arkinson ◽  
Viduth K. Chaugule ◽  
Mairi Clarke ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Large Scale ◽  
The Other ◽  
Molecular Function ◽  
Post Translational Modifications ◽  
Hydrophobic Residues ◽  
Interstrand Crosslinks ◽  
Double Stranded Dna ◽  
Dna Interstrand Crosslinks ◽  
Lysine Residues

AbstractThe Fanconi Anemia (FA) pathway is a dedicated pathway for the repair of DNA interstrand crosslinks, and which is additionally activated in response to other forms of replication stress. A key step in the activation of the FA pathway is the monoubiquitination of each of the two subunits (FANCI and FANCD2) of the ID2 complex on specific lysine residues. However, the molecular function of these modifications has been unknown for nearly two decades. Here we find that ubiquitination of FANCD2 acts to increase ID2’s affinity for double stranded DNA via promoting/stabilizing a large-scale conformational change in the complex, resulting in a secondary “Arm” ID2 interphase encircling DNA. Ubiquitination of FANCI, on the other hand, largely protects the ubiquitin on FANCD2 from USP1/UAF deubiquitination, with key hydrophobic residues of FANCI’s ubiquitin being important for this protection. In effect, both of these post-translational modifications function to stabilise a conformation in which the ID2 complex encircles DNA.

scholarly journals FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks

2016 ◽  
Vol 44 (7) ◽  
pp. 3219-3232 ◽  
Author(s):  
Florian Rohleder ◽  
Jing Huang ◽  
Yutong Xue ◽  
Jochen Kuper ◽  
Adam Round ◽  
...  
Keyword(s):  
Interstrand Crosslinks ◽  
Dna Interstrand Crosslinks

scholarly journals Enhanced repair of DNA interstrand crosslinks in S phase

FEBS Letters ◽  
2006 ◽  
Vol 580 (6) ◽  
pp. 1631-1634 ◽  
Author(s):  
Veronika Mladenova ◽  
George Russev
Keyword(s):  
S Phase ◽  
Interstrand Crosslinks ◽  
Dna Interstrand Crosslinks

scholarly journals Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks

2009 ◽  
Vol 37 (13) ◽  
pp. 4420-4429 ◽  
Author(s):  
Junhua Zhao ◽  
Aklank Jain ◽  
Ravi R. Iyer ◽  
Paul L. Modrich ◽  
Karen M. Vasquez
Keyword(s):  
Mismatch Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Interstrand Crosslinks ◽  
Dna Interstrand Crosslinks ◽  
Nucleotide Excision
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