FAN1 Activity on Asymmetric Repair Intermediates is Mediated by an Atypical Monomeric Virus-type Replication-repair Nuclease Domain

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2014 Jul 2

PMID 24981866

Citations 12

Authors

Simon Pennell

Anne-Cecile Declais

Jiejin Li

Lesley F Haire

Wioletta Berg

Jose W Saldanha

Ian A Taylor

John Rouse

David M J Lilley

Stephen J Smerdon

Affiliations

Soon will be listed here.

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.

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References

Kee Y, DAndrea A . Expanded roles of the Fanconi anemia pathway in preserving genomic stability. Genes Dev. 2010; 24(16):1680-94. PMC: 2922498. DOI: 10.1101/gad.1955310. View

Ionita-Laza I, Xu B, Makarov V, Buxbaum J, Roos J, Gogos J . Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism. Proc Natl Acad Sci U S A. 2013; 111(1):343-8. PMC: 3890869. DOI: 10.1073/pnas.1309475110. View

White M, Giraud-Panis M, Pohler J, Lilley D . Recognition and manipulation of branched DNA structure by junction-resolving enzymes. J Mol Biol. 1997; 269(5):647-64. DOI: 10.1006/jmbi.1997.1097. View

McGuffin L, Bryson K, Jones D . The PSIPRED protein structure prediction server. Bioinformatics. 2000; 16(4):404-5. DOI: 10.1093/bioinformatics/16.4.404. View

Sharples G, Curtis F, McGlynn P, Bolt E . Holliday junction binding and resolution by the Rap structure-specific endonuclease of phage lambda. J Mol Biol. 2004; 340(4):739-51. DOI: 10.1016/j.jmb.2004.05.030. View

Kottemann M, Smogorzewska A . Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature. 2013; 493(7432):356-63. PMC: 3700363. DOI: 10.1038/nature11863. View

Iyer L, Babu M, Aravind L . The HIRAN domain and recruitment of chromatin remodeling and repair activities to damaged DNA. Cell Cycle. 2006; 5(7):775-82. DOI: 10.4161/cc.5.7.2629. View

Zhou W, Otto E, Cluckey A, Airik R, Hurd T, Chaki M . FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair. Nat Genet. 2012; 44(8):910-5. PMC: 3412140. DOI: 10.1038/ng.2347. View

Bond C, Kvaratskhelia M, Richard D, White M, Hunter W . Structure of Hjc, a Holliday junction resolvase, from Sulfolobus solfataricus. Proc Natl Acad Sci U S A. 2001; 98(10):5509-14. PMC: 33243. DOI: 10.1073/pnas.091613398. View

10.

Castor D, Nair N, Declais A, Lachaud C, Toth R, Macartney T . Cooperative control of holliday junction resolution and DNA repair by the SLX1 and MUS81-EME1 nucleases. Mol Cell. 2013; 52(2):221-33. PMC: 3808987. DOI: 10.1016/j.molcel.2013.08.036. View

11.

Kratz K, Schopf B, Kaden S, Sendoel A, Eberhard R, Lademann C . Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell. 2010; 142(1):77-88. DOI: 10.1016/j.cell.2010.06.022. View

12.

Steczkiewicz K, Muszewska A, Knizewski L, Rychlewski L, Ginalski K . Sequence, structure and functional diversity of PD-(D/E)XK phosphodiesterase superfamily. Nucleic Acids Res. 2012; 40(15):7016-45. PMC: 3424549. DOI: 10.1093/nar/gks382. View

13.

Jones D . Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol. 1999; 292(2):195-202. DOI: 10.1006/jmbi.1999.3091. View

14.

Sali A, Blundell T . Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol. 1993; 234(3):779-815. DOI: 10.1006/jmbi.1993.1626. View

15.

Harrington J, Lieber M . The characterization of a mammalian DNA structure-specific endonuclease. EMBO J. 1994; 13(5):1235-46. PMC: 394933. DOI: 10.1002/j.1460-2075.1994.tb06373.x. View

16.

Simossis V, Heringa J . PRALINE: a multiple sequence alignment toolbox that integrates homology-extended and secondary structure information. Nucleic Acids Res. 2005; 33(Web Server issue):W289-94. PMC: 1160151. DOI: 10.1093/nar/gki390. View

17.

Nishino T, Komori K, Tsuchiya D, Ishino Y, Morikawa K . Crystal structure of the archaeal holliday junction resolvase Hjc and implications for DNA recognition. Structure. 2001; 9(3):197-204. DOI: 10.1016/s0969-2126(01)00576-7. View

18.

Knizewski L, Kinch L, Grishin N, Rychlewski L, Ginalski K . Realm of PD-(D/E)XK nuclease superfamily revisited: detection of novel families with modified transitive meta profile searches. BMC Struct Biol. 2007; 7:40. PMC: 1913061. DOI: 10.1186/1472-6807-7-40. View

19.

Brown P, Schuck P . Macromolecular size-and-shape distributions by sedimentation velocity analytical ultracentrifugation. Biophys J. 2006; 90(12):4651-61. PMC: 1471869. DOI: 10.1529/biophysj.106.081372. View

20.

Tsutakawa S, Classen S, Chapados B, Arvai A, Finger L, Guenther G . Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily. Cell. 2011; 145(2):198-211. PMC: 3086263. DOI: 10.1016/j.cell.2011.03.004. View