About: Structural Insights into 5' Flap DNA Unwinding and Incision by the Human FAN1 Dimer

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About: Structural Insights into 5' Flap DNA Unwinding and Incision by the Human FAN1 Dimer Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Structural Insights into 5' Flap DNA Unwinding and Incision by the Human FAN1 Dimer
Source	Medline; PMC
abstract	Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5’ flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA, and unwind a 5’ flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation, or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1.
has issue date	2014-12-11(xsd:dateTime)
bibo:doi	10.1038/ncomms6726
bibo:pmid	25500724
has license	no-cc
sha1sum (hex)	04fb1656b773a1db9bc2b340aa503fe12132c670
schema:url	https://doi.org/10.1038/ncomms6726
resource representing a document's title	Structural Insights into 5' Flap DNA Unwinding and Incision by the Human FAN1 Dimer
has PubMed Central identifier	PMC4268874
has PubMed identifier	25500724
schema:publication	Nat Commun
resource representing a document's body	covid:04fb1656b773a1db9bc2b340aa503fe12132c670#body_text
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