3zdk

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[[Image:3zdk.jpg|left|200px]]
 
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{{STRUCTURE_3zdk| PDB=3zdk | SCENE= }}
{{STRUCTURE_3zdk| PDB=3zdk | SCENE= }}
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===Crystal structure of human 5' exonuclease Apollo===
===Crystal structure of human 5' exonuclease Apollo===
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==Disease==
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[[http://www.uniprot.org/uniprot/DCR1B_HUMAN DCR1B_HUMAN]] Defects in DCLRE1B may be a cause of Hoyeraal-Hreidarsson syndrome (HHS) [MIM:[http://omim.org/entry/300240 300240]]. HHS is a multisystem disorder affecting males and is characterized by aplastic anemia, immunodeficiency, microcephaly, cerebellar hypoplasia, and growth retardation. Note=An aberrant splice variant designated Apollo-Delta has been found in a patient with Hoyeraal-Hreidarsson syndrome. Apollo-Delta hampers the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome.<ref>PMID:20479256</ref>
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==Function==
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[[http://www.uniprot.org/uniprot/DCR1B_HUMAN DCR1B_HUMAN]] 5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint.<ref>PMID:15572677</ref><ref>PMID:15467758</ref><ref>PMID:16730176</ref><ref>PMID:16730175</ref><ref>PMID:18468965</ref><ref>PMID:18469862</ref><ref>PMID:19197158</ref><ref>PMID:19411856</ref><ref>PMID:20655466</ref>
==About this Structure==
==About this Structure==
[[3zdk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDK OCA].
[[3zdk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDK OCA].
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==Reference==
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<references group="xtra"/><references/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Allerston, C K.]]
[[Category: Allerston, C K.]]

Revision as of 23:41, 24 March 2013

Template:STRUCTURE 3zdk

Contents

Crystal structure of human 5' exonuclease Apollo

Disease

[DCR1B_HUMAN] Defects in DCLRE1B may be a cause of Hoyeraal-Hreidarsson syndrome (HHS) [MIM:300240]. HHS is a multisystem disorder affecting males and is characterized by aplastic anemia, immunodeficiency, microcephaly, cerebellar hypoplasia, and growth retardation. Note=An aberrant splice variant designated Apollo-Delta has been found in a patient with Hoyeraal-Hreidarsson syndrome. Apollo-Delta hampers the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome.[1]

Function

[DCR1B_HUMAN] 5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint.[2][3][4][5][6][7][8][9][10]

About this Structure

3zdk is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  1. ↑ Touzot F, Callebaut I, Soulier J, Gaillard L, Azerrad C, Durandy A, Fischer A, de Villartay JP, Revy P. Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal-Hreidarsson syndrome. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10097-102. doi:, 10.1073/pnas.0914918107. Epub 2010 May 17. PMID:20479256 doi:10.1073/pnas.0914918107
  2. ↑ Ishiai M, Kimura M, Namikoshi K, Yamazoe M, Yamamoto K, Arakawa H, Agematsu K, Matsushita N, Takeda S, Buerstedde JM, Takata M. DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation. Mol Cell Biol. 2004 Dec;24(24):10733-41. PMID:15572677 doi:24/24/10733
  3. ↑ Demuth I, Digweed M, Concannon P. Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation. Oncogene. 2004 Nov 11;23(53):8611-8. PMID:15467758 doi:1207895
  4. ↑ van Overbeek M, de Lange T. Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase. Curr Biol. 2006 Jul 11;16(13):1295-302. Epub 2006 May 25. PMID:16730176 doi:10.1016/j.cub.2006.05.022
  5. ↑ Lenain C, Bauwens S, Amiard S, Brunori M, Giraud-Panis MJ, Gilson E. The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair. Curr Biol. 2006 Jul 11;16(13):1303-10. Epub 2006 May 25. PMID:16730175 doi:10.1016/j.cub.2006.05.021
  6. ↑ Demuth I, Bradshaw PS, Lindner A, Anders M, Heinrich S, Kallenbach J, Schmelz K, Digweed M, Meyn MS, Concannon P. Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation. DNA Repair (Amst). 2008 Aug 2;7(8):1192-201. doi: 10.1016/j.dnarep.2008.03.020., Epub 2008 May 12. PMID:18468965 doi:10.1016/j.dnarep.2008.03.020
  7. ↑ Bae JB, Mukhopadhyay SS, Liu L, Zhang N, Tan J, Akhter S, Liu X, Shen X, Li L, Legerski RJ. Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand cross-links. Oncogene. 2008 Aug 28;27(37):5045-56. doi: 10.1038/onc.2008.139. Epub 2008 May, 12. PMID:18469862 doi:10.1038/onc.2008.139
  8. ↑ Liu L, Akhter S, Bae JB, Mukhopadhyay SS, Richie CT, Liu X, Legerski R. SNM1B/Apollo interacts with astrin and is required for the prophase cell cycle checkpoint. Cell Cycle. 2009 Feb 15;8(4):628-38. Epub 2009 Feb 7. PMID:19197158
  9. ↑ Anders M, Mattow J, Digweed M, Demuth I. Evidence for hSNM1B/Apollo functioning in the HSP70 mediated DNA damage response. Cell Cycle. 2009 Jun 1;8(11):1725-32. Epub 2009 Jun 1. PMID:19411856
  10. ↑ Ye J, Lenain C, Bauwens S, Rizzo A, Saint-Leger A, Poulet A, Benarroch D, Magdinier F, Morere J, Amiard S, Verhoeyen E, Britton S, Calsou P, Salles B, Bizard A, Nadal M, Salvati E, Sabatier L, Wu Y, Biroccio A, Londono-Vallejo A, Giraud-Panis MJ, Gilson E. TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage. Cell. 2010 Jul 23;142(2):230-42. doi: 10.1016/j.cell.2010.05.032. PMID:20655466 doi:10.1016/j.cell.2010.05.032

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