4m7c

From Proteopedia

Revision as of 08:07, 29 September 2013 by OCA (Talk | contribs)
Jump to: navigation, search

Template:STRUCTURE 4m7c

Contents

Crystal structure of the TRF2-binding motif of SLX4 in complex with the TRFH domain of TRF2

Template:ABSTRACT PUBMED 24012755

Disease

[SLX4_HUMAN] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry.

Function

[TERF2_HUMAN] Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.[1] [2] [3] [SLX4_HUMAN] Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks.[4] [5] [6] [7]

About this Structure

4m7c is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Wan B, Yin J, Horvath K, Sarkar J, Chen Y, Wu J, Wan K, Lu J, Gu P, Yu EY, Lue NF, Chang S, Liu Y, Lei M. SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres. Cell Rep. 2013 Sep 12;4(5):861-869. doi: 10.1016/j.celrep.2013.08.017. Epub 2013 , Sep 5. PMID:24012755 doi:10.1016/j.celrep.2013.08.017
  1. ↑ van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998 Feb 6;92(3):401-13. PMID:9476899
  2. ↑ de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005 Sep 15;19(18):2100-10. PMID:16166375 doi:10.1101/gad.1346005
  3. ↑ 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
  4. ↑ Svendsen JM, Smogorzewska A, Sowa ME, O'Connell BC, Gygi SP, Elledge SJ, Harper JW. Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell. 2009 Jul 10;138(1):63-77. PMID:19596235 doi:S0092-8674(09)00777-6
  5. ↑ Fekairi S, Scaglione S, Chahwan C, Taylor ER, Tissier A, Coulon S, Dong MQ, Ruse C, Yates JR 3rd, Russell P, Fuchs RP, McGowan CH, Gaillard PH. Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell. 2009 Jul 10;138(1):78-89. PMID:19596236 doi:S0092-8674(09)00776-4
  6. ↑ Munoz IM, Hain K, Declais AC, Gardiner M, Toh GW, Sanchez-Pulido L, Heuckmann JM, Toth R, Macartney T, Eppink B, Kanaar R, Ponting CP, Lilley DM, Rouse J. Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. Mol Cell. 2009 Jul 10;35(1):116-27. PMID:19595721 doi:S1097-2765(09)00433-X
  7. ↑ Andersen SL, Bergstralh DT, Kohl KP, LaRocque JR, Moore CB, Sekelsky J. Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombination. Mol Cell. 2009 Jul 10;35(1):128-35. PMID:19595722 doi:S1097-2765(09)00432-8

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4m7c"
Personal tools