Crystal Structures of Aprataxin Ortholog Hnt3 Reveal the Mechanism for Reversal of 5'-adenylated DNA

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2011 Oct 11

PMID 21984208

Citations 5

Authors

Yong Gong

Deyu Zhu

Jingjin Ding

Chuan-Na Dou

Xiaoming Ren

Lichuan Gu

Tao Jiang

Da-Cheng Wang

Affiliations

Soon will be listed here.

Abstract

Aprataxin is a DNA deadenylase that resolves DNA 5'-AMP termini and reverses abortive DNA ligation. The crystal structures of Schizosaccharomyces pombe aprataxin Hnt3 in its apo form and in complex to dsDNA and dsDNA-AMP reveal how Hnt3 recognizes and processes 5'-adenylated DNA in a structure-specific manner. The bound DNA adopts a 5'-flap conformation that facilitates 5'-AMP access to the active site, where AMP cleavage occurs by a canonical catalytic mechanism.

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References

Kijas A, Harris J, Harris J, Lavin M . Aprataxin forms a discrete branch in the HIT (histidine triad) superfamily of proteins with both DNA/RNA binding and nucleotide hydrolase activities. J Biol Chem. 2006; 281(20):13939-48. DOI: 10.1074/jbc.M507946200. View

Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S . Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat Genet. 2001; 29(2):184-8. DOI: 10.1038/ng1001-184. View

Moreira M, Barbot C, Tachi N, Kozuka N, Uchida E, Gibson T . The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nat Genet. 2001; 29(2):189-93. DOI: 10.1038/ng1001-189. View

Caldecott K . Single-strand break repair and genetic disease. Nat Rev Genet. 2008; 9(8):619-31. DOI: 10.1038/nrg2380. View

Aicardi J, Barbosa C, Andermann E, Andermann F, Morcos R, Ghanem Q . Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia. Ann Neurol. 1988; 24(4):497-502. DOI: 10.1002/ana.410240404. View

Clements P, Breslin C, Deeks E, Byrd P, Ju L, Bieganowski P . The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. DNA Repair (Amst). 2004; 3(11):1493-502. DOI: 10.1016/j.dnarep.2004.06.017. View

Wolfe S, Nekludova L, Pabo C . DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct. 2000; 29:183-212. DOI: 10.1146/annurev.biophys.29.1.183. View

Ahel I, Rass U, El-Khamisy S, Katyal S, Clements P, McKinnon P . The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature. 2006; 443(7112):713-6. DOI: 10.1038/nature05164. View

Rass U, Ahel I, West S . Molecular mechanism of DNA deadenylation by the neurological disease protein aprataxin. J Biol Chem. 2008; 283(49):33994-4001. PMC: 2662222. DOI: 10.1074/jbc.M807124200. View

10.

Sykora P, Croteau D, Bohr V, Wilson 3rd D . Aprataxin localizes to mitochondria and preserves mitochondrial function. Proc Natl Acad Sci U S A. 2011; 108(18):7437-42. PMC: 3088601. DOI: 10.1073/pnas.1100084108. View

11.

Brenner C . Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. Biochemistry. 2002; 41(29):9003-14. PMC: 2571077. DOI: 10.1021/bi025942q. View

12.

Rass U, Ahel I, West S . Actions of aprataxin in multiple DNA repair pathways. J Biol Chem. 2007; 282(13):9469-9474. DOI: 10.1074/jbc.M611489200. View

13.

Deshpande G, Hayles J, Hoe K, Kim D, Park H, Hartsuiker E . Screening a genome-wide S. pombe deletion library identifies novel genes and pathways involved in genome stability maintenance. DNA Repair (Amst). 2009; 8(5):672-9. PMC: 2675035. DOI: 10.1016/j.dnarep.2009.01.016. View

14.

Lima C, Klein M, Hendrickson W . Structure-based analysis of catalysis and substrate definition in the HIT protein family. Science. 1997; 278(5336):286-90. DOI: 10.1126/science.278.5336.286. View

15.

Rass U, Ahel I, West S . Defective DNA repair and neurodegenerative disease. Cell. 2007; 130(6):991-1004. DOI: 10.1016/j.cell.2007.08.043. View

16.

Becherel O, Jakob B, Cherry A, Gueven N, Fusser M, Kijas A . CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response. Nucleic Acids Res. 2009; 38(5):1489-503. PMC: 2836575. DOI: 10.1093/nar/gkp1149. View