| Structural highlights
Function
MUS81_HUMAN Interacts with EME1 and EME2 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
MUS81 is an important structure-specific endonuclease responsible for the processing of stalled replication forks and recombination intermediates. In human, MUS81 functions by forming complexes with its regulatory subunits EME1 and EME2, playing distinct roles in G2/M and S phases. Although the structures of MUS81-EME1 have been intensively studied, there is no structure information available about MUS81-EME2. Here, we report the crystal structure of MUS81-EME2, which reveals an overall protein fold similar to that of MUS81-EME1 complex. Further biochemical and structural characterization shows that the MUS81-EME1 and MUS81-EME2 complexes are identical in substrate recognition and endonuclease activities in vitro, implying that the distinct cellular roles of the two complexes could arise from temporal controls in cells. Finally, an extensive structure-guided mutagenesis analysis provides implications for the molecular basis of how the MUS81-EME endonucleases recognize various DNA substrates in a structure-selective manner.
Crystal structure of the human MUS81-EME2 complex.,Hua Z, Fang Q, Zhang D, Luo Z, Yuan C, Lin Z Structure. 2022 May 5;30(5):743-752.e3. doi: 10.1016/j.str.2022.02.015. Epub 2022 , Mar 14. PMID:35290797[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen XB, Melchionna R, Denis CM, Gaillard PH, Blasina A, Van de Weyer I, Boddy MN, Russell P, Vialard J, McGowan CH. Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Mol Cell. 2001 Nov;8(5):1117-27. PMID:11741546
- ↑ Constantinou A, Chen XB, McGowan CH, West SC. Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificities. EMBO J. 2002 Oct 15;21(20):5577-85. PMID:12374758
- ↑ Ogrunc M, Sancar A. Identification and characterization of human MUS81-MMS4 structure-specific endonuclease. J Biol Chem. 2003 Jun 13;278(24):21715-20. Epub 2003 Apr 9. PMID:12686547 doi:https://dx.doi.org/10.1074/jbc.M302484200
- ↑ Ciccia A, Constantinou A, West SC. Identification and characterization of the human mus81-eme1 endonuclease. J Biol Chem. 2003 Jul 4;278(27):25172-8. Epub 2003 Apr 29. PMID:12721304 doi:https://dx.doi.org/10.1074/jbc.M302882200
- ↑ Blais V, Gao H, Elwell CA, Boddy MN, Gaillard PH, Russell P, McGowan CH. RNA interference inhibition of Mus81 reduces mitotic recombination in human cells. Mol Biol Cell. 2004 Feb;15(2):552-62. Epub 2003 Nov 14. PMID:14617801 doi:https://dx.doi.org/10.1091/mbc.E03-08-0580
- ↑ Zhang R, Sengupta S, Yang Q, Linke SP, Yanaihara N, Bradsher J, Blais V, McGowan CH, Harris CC. BLM helicase facilitates Mus81 endonuclease activity in human cells. Cancer Res. 2005 Apr 1;65(7):2526-31. PMID:15805243 doi:https://dx.doi.org/10.1158/0008-5472.CAN-04-2421
- ↑ Ciccia A, Ling C, Coulthard R, Yan Z, Xue Y, Meetei AR, Laghmani el H, Joenje H, McDonald N, de Winter JP, Wang W, West SC. Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM. Mol Cell. 2007 Feb 9;25(3):331-43. PMID:17289582 doi:https://dx.doi.org/S1097-2765(07)00007-X
- ↑ 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
- ↑ 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
- ↑ Hua Z, Fang Q, Zhang D, Luo Z, Yuan C, Lin Z. Crystal structure of the human MUS81-EME2 complex. Structure. 2022 May 5;30(5):743-752.e3. PMID:35290797 doi:10.1016/j.str.2022.02.015
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