Cellular response to DNA interstrand crosslinks: the Fanconi anemia pathway

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Snm1B/Apollo functions in the Fanconi anemia pathway in response to DNA interstrand crosslinks.

Fanconi anemia (FA) is an inherited chromosomal instability disorder characterized by childhood aplastic anemia, developmental abnormalities and cancer predisposition. One of the hallmark phenotypes of FA is cellular hypersensitivity to agents that induce DNA interstrand crosslinks (ICLs), such as mitomycin C (MMC). FA is caused by mutation in at least 14 genes which function in the resolution ...

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UHRF1 Is a Sensor for DNA Interstrand Crosslinks and Recruits FANCD2 to Initiate the Fanconi Anemia Pathway

The Fanconi anemia (FA) pathway is critical for the cellular response to toxic DNA interstrand crosslinks (ICLs). Using a biochemical purification strategy, we identified UHRF1 as a protein that specifically interacts with ICLs in vitro and in vivo. Reduction of cellular levels of UHRF1 by RNAi attenuates the FA pathway and sensitizes cells to mitomycin C. Knockdown cells display a drastic redu...

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AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, ...

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Hsp90 regulates the Fanconi anemia DNA damage response pathway.

Heat shock protein 90 (Hsp90) regulates diverse signaling pathways. Emerging evidence suggests that Hsp90 inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), enhance DNA damage-induced cell death, suggesting that Hsp90 may regulate cellular responses to genotoxic stress. However, the underlying mechanisms are poorly understood. Here, we show that the Fanconi anemia (FA) pathway...

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The 13th Fanconi Anemia Gene Identified: FANCI – Importance of the ‘Fanconi Anemia Pathway’ for Cellular Oncology

After quite some scientific debate over the last decade, it has become evident that chromosomal instability is a major driving force in the pathogenesis of the vast majority of human cancers [1–3]. In addition, different patterns of chromosomal instability appear to have different clinical implications [4,5]. Yet, unlike for the less common form of genomic instability caused by failing DNA mism...

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ژورنال

عنوان ژورنال: Cellular and Molecular Life Sciences

سال: 2016

ISSN: 1420-682X,1420-9071

DOI: 10.1007/s00018-016-2218-x