ArticleCell cycle (Georgetown, Tex.)2015
Decarbamoyl mitomycin C (DMC) activates p53-independent ataxia telangiectasia and rad3 related protein (ATR) chromatin eviction.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Stereoisomeric mitomycins interstrand crosslinks differently impact gene expression in MCF-7 and K562 cancer cells.Chemico-biological interactions · 2025Article
- Mitomycin C and its analog trigger cytotoxicity in MCF-7 and K562 cancer cells through the regulation of RAS and MAPK/ERK pathways.Chemico-biological interactions · 2024Article
- Immunohistochemical Pattern of Histone H2A Variant Expression in an Experimental Model of Ischemia-Reperfusion-Induced Acute Kidney Injury.International journal of molecular sciences · 2023Article
- Insight Into Factors Governing Formation, Synthesis and Stereochemical Configuration of DNA Adducts Formed by Mitomycins.Chemical record (New York, N.Y.) · 2023Review
- Cytotoxicity, crosslinking and biological activity of three mitomycins.Bioorganic chemistry · 2022Article
- Synthesis of Oligonucleotides containing the cis-Interstrand Crosslink Produced by Mitomycins in their Reaction with DNA.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Interdependent Sequence Selectivity and Diastereoselectivity in the Alkylation of DNA by Decarbamoylmitomycin C.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Isolation and Rationale for the Formation of Isomeric Decarbamoylmitomycin C- NChemical research in toxicology · 2018Article
- Sequence-Dependent Diastereospecific and Diastereodivergent Crosslinking of DNA by Decarbamoylmitomycin C.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- DNA repair in ischemic acute kidney injury.American journal of physiology. Renal physiology · 2017Review
- Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation.International journal of oncology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Interstrand crosslinks induce DNA replication fork stalling that in turn activates the ATR-dependent checkpoint and DNA repair on nuclear chromatin. Mitomycin C (MC) and Decarbamoyl Mitomycin C (DMC) induce different types of DNA crosslinks with DMC being a more cytotoxic agent. We previously reported that the novel DMC induced β-interstrand DNA crosslinks induce a p53-independent form of cell death. The p53-independent DMC cytotoxicity associates with the activation, and subsequent depletion, of Chk1. In this study we further dissect the novel DMC signal transduction pathway and asked how it influences chromatin-associated proteins. We found that treatment with DMC, but not MC, stimulated the disassociation of ATR from chromatin and re-localization of ATR to the cytoplasm. The chromatin eviction of ATR was coupled with the formation of nuclear Rad51 foci and the phosphorylation of Chk1. Furthermore, DMC but not MC, activated expression of gadd45α mRNA. Importantly, knocking down p53 via shRNA did not inhibit the DMC-induced disassociation of ATR from chromatin or reduce the activation of transcription of gadd45α. Our results suggest that DMC induces a p53-independent disassociation of ATR from chromatin that facilitates Chk1 checkpoint activation and Rad51 chromatin recruitment. Our findings provide evidence that ATR chromatin eviction in breast cancer cells is an area of study that should be focused on for inducing p53-independent cell death.
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