FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain

Simon Pennell; Anne-Cécile Déclais; Jiejin Li; Lesley F. Haire; Wioletta Berg; José W. Saldanha; Ian A. Taylor; John Rouse; David M. J. Lilley; Stephen J. Smerdon

doi:10.1016/j.celrep.2014.06.001

FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain

Simon Pennell (Lead / Corresponding author), Anne-Cécile Déclais, Jiejin Li, Lesley F. Haire, Wioletta Berg, José W. Saldanha, Ian A. Taylor, John Rouse, David M. J. Lilley, Stephen J. Smerdon

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Abstract

FAN1 is a structure-selective DNA repair nuclease with 5' flap endonuclease activity, involved in the repair of interstrand DNA crosslinks. It is the only eukaryotic protein with a virus-type replication-repair nuclease ("VRR-Nuc") "module" that commonly occurs as a standalone domain in many bacteria and viruses. Crystal structures of three representatives show that they structurally resemble Holliday junction resolvases (HJRs), are dimeric in solution, and are able to cleave symmetric four-way junctions. In contrast, FAN1 orthologs are monomeric and cleave 5' flap structures in vitro, but not Holliday junctions. Modeling of the VRR-Nuc domain of FAN1 reveals that it has an insertion, which packs against the dimerization interface observed in the structures of the viral/bacterial VRR-Nuc proteins. We propose that these additional structural elements in FAN1 prevent dimerization and bias specificity toward flap structures.

Original language	English
Pages (from-to)	84-93
Number of pages	10
Journal	Cell Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2014.06.001
Publication status	Published - 10 Jul 2014

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10.1016/j.celrep.2014.06.001

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©2014 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). You may distribute and copy the article, create extracts, abstracts, and other revised versions, adaptations or derivative works of or from an article (such as a translation), to include in a collective work (such as an anthology), to text or data mine the article, including for commercial purposes without permission from Elsevier. The original work must always be appropriately credited.
Final published version, 2.74 MBLicence: CC BY

Fluorescence Resonance Energy Transfer as a Rich Source of Orientational Information in Nucleic Acid Structure
Lilley, D. (Investigator)
Engineering and Physical Sciences Research Council
1/09/12 → 30/06/16
Project: Research

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title = "FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain",

abstract = "FAN1 is a structure-selective DNA repair nuclease with 5' flap endonuclease activity, involved in the repair of interstrand DNA crosslinks. It is the only eukaryotic protein with a virus-type replication-repair nuclease ({"}VRR-Nuc{"}) {"}module{"} that commonly occurs as a standalone domain in many bacteria and viruses. Crystal structures of three representatives show that they structurally resemble Holliday junction resolvases (HJRs), are dimeric in solution, and are able to cleave symmetric four-way junctions. In contrast, FAN1 orthologs are monomeric and cleave 5' flap structures in vitro, but not Holliday junctions. Modeling of the VRR-Nuc domain of FAN1 reveals that it has an insertion, which packs against the dimerization interface observed in the structures of the viral/bacterial VRR-Nuc proteins. We propose that these additional structural elements in FAN1 prevent dimerization and bias specificity toward flap structures.",

author = "Simon Pennell and Anne-C{\'e}cile D{\'e}clais and Jiejin Li and Haire, {Lesley F.} and Wioletta Berg and Saldanha, {Jos{\'e} W.} and Taylor, {Ian A.} and John Rouse and Lilley, {David M. J.} and Smerdon, {Stephen J.}",

year = "2014",

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doi = "10.1016/j.celrep.2014.06.001",

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T1 - FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain

AU - Pennell, Simon

AU - Déclais, Anne-Cécile

AU - Li, Jiejin

AU - Haire, Lesley F.

AU - Berg, Wioletta

AU - Saldanha, José W.

AU - Taylor, Ian A.

AU - Rouse, John

AU - Lilley, David M. J.

AU - Smerdon, Stephen J.

PY - 2014/7/10

Y1 - 2014/7/10

N2 - FAN1 is a structure-selective DNA repair nuclease with 5' flap endonuclease activity, involved in the repair of interstrand DNA crosslinks. It is the only eukaryotic protein with a virus-type replication-repair nuclease ("VRR-Nuc") "module" that commonly occurs as a standalone domain in many bacteria and viruses. Crystal structures of three representatives show that they structurally resemble Holliday junction resolvases (HJRs), are dimeric in solution, and are able to cleave symmetric four-way junctions. In contrast, FAN1 orthologs are monomeric and cleave 5' flap structures in vitro, but not Holliday junctions. Modeling of the VRR-Nuc domain of FAN1 reveals that it has an insertion, which packs against the dimerization interface observed in the structures of the viral/bacterial VRR-Nuc proteins. We propose that these additional structural elements in FAN1 prevent dimerization and bias specificity toward flap structures.

AB - FAN1 is a structure-selective DNA repair nuclease with 5' flap endonuclease activity, involved in the repair of interstrand DNA crosslinks. It is the only eukaryotic protein with a virus-type replication-repair nuclease ("VRR-Nuc") "module" that commonly occurs as a standalone domain in many bacteria and viruses. Crystal structures of three representatives show that they structurally resemble Holliday junction resolvases (HJRs), are dimeric in solution, and are able to cleave symmetric four-way junctions. In contrast, FAN1 orthologs are monomeric and cleave 5' flap structures in vitro, but not Holliday junctions. Modeling of the VRR-Nuc domain of FAN1 reveals that it has an insertion, which packs against the dimerization interface observed in the structures of the viral/bacterial VRR-Nuc proteins. We propose that these additional structural elements in FAN1 prevent dimerization and bias specificity toward flap structures.

U2 - 10.1016/j.celrep.2014.06.001

DO - 10.1016/j.celrep.2014.06.001

M3 - Article

C2 - 24981866

SN - 2211-1247

VL - 8

SP - 84

EP - 93

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain

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Fluorescence Resonance Energy Transfer as a Rich Source of Orientational Information in Nucleic Acid Structure

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