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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34987

Kratz, K; Schöpf, B; Kaden, S; Sendoel, A; Eberhard, R; Lademann, C; Cannavó, E; Sartori, A A; Hengartner, M O; Jiricny, J (2010). Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell, 142(1):77-88.

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Abstract

Cytotoxicity of cisplatin and mitomycin C (MMC) is ascribed largely to their ability to generate interstrand crosslinks (ICLs) in DNA, which block the progression of replication forks. The processing of ICLs requires the Fanconi anemia (FA) pathway, excision repair, and translesion DNA synthesis (TLS). It also requires homologous recombination (HR), which repairs double-strand breaks (DSBs) generated by cleavage of the blocked replication forks. Here we describe KIAA1018, an evolutionarily conserved protein that has an N-terminal ubiquitin-binding zinc finger (UBZ) and a C-terminal nuclease domain. KIAA1018 is a 5'-->3' exonuclease and a structure-specific endonuclease that preferentially incises 5' flaps. Like cells from FA patients, human cells depleted of KIAA1018 are sensitized to ICL-inducing agents and display chromosomal instability. The link of KIAA1018 to the FA pathway is further strengthened by its recruitment to DNA damage through interaction of its UBZ domain with monoubiquitylated FANCD2. We therefore propose to name KIAA1018 FANCD2-associated nuclease, FAN1.

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106 citations in Web of Science®
109 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
DDC:570 Life sciences; biology
Language:English
Date:2010
Deposited On:16 Jul 2010 13:18
Last Modified:23 Dec 2013 11:34
Publisher:Elsevier
ISSN:0092-8674
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1016/j.cell.2010.06.022
PubMed ID:20603016

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