Roles of SLX1–SLX4, MUS81–EME1, and GEN1 in avoiding genome instability and mitotic catastrophe

The resolution of recombination intermediates containing Holliday junctions (HJs) is critical for genome maintenance. Three pathways for HJ processing involve the BTR complex, the SLX–MUS complex, and GEN1. It has been suggested that SLX–MUS and GEN1 provide backup resolution pathways during mitosis. West and colleagues now show that cells lacking SLX–MUS and GEN1 exhibit impaired replication fork progression and chromosome instability. Furthermore, the effects of SLX4, MUS81, and GEN1 depletion extend throughout the cell cycle, revealing vital and expansive functions for these factors in genome integrity.

[1]  D. Lilley,et al.  Cooperative Control of Holliday Junction Resolution and DNA Repair by the SLX1 and MUS81-EME1 Nucleases , 2013, Molecular cell.

[2]  S. West,et al.  Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells. , 2013, Molecular cell.

[3]  Molly C. Kottemann,et al.  Human GEN1 and the SLX4-associated nucleases MUS81 and SLX1 are essential for the resolution of replication-induced Holliday junctions. , 2013, Cell reports.

[4]  S. West,et al.  Cell-cycle kinases coordinate the resolution of recombination intermediates with chromosome segregation. , 2013, Cell reports.

[5]  Y. Liu,et al.  MUS81 promotes common fragile site expression , 2013, Nature Cell Biology.

[6]  F. Rosselli,et al.  ERCC1 and MUS81–EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis , 2013, Nature Cell Biology.

[7]  A. Auerbach,et al.  Regulation of multiple DNA repair pathways by the Fanconi anemia protein SLX4. , 2013, Blood.

[8]  I. Demuth,et al.  The nuclease hSNM1B/Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP/SLX4. , 2012, Human molecular genetics.

[9]  I. Demuth,et al.  The nuclease hSNM 1 B / Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP / SLX 4 , 2012 .

[10]  I. Hickson,et al.  New insights into the formation and resolution of ultra-fine anaphase bridges. , 2011, Seminars in cell & developmental biology.

[11]  J. Sekelsky,et al.  Three Structure-Selective Endonucleases Are Essential in the Absence of BLM Helicase in Drosophila , 2011, PLoS genetics.

[12]  S. West,et al.  Regulatory Control of the Resolution of DNA Recombination Intermediates during Meiosis and Mitosis , 2011, Cell.

[13]  C. Bradshaw,et al.  Replication stress induces 53BP1-containing OPT domains in G1 cells , 2011, The Journal of cell biology.

[14]  S. West,et al.  Aberrant chromosome morphology in human cells defective for Holliday junction resolution , 2011, Nature.

[15]  B. Neumann,et al.  53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress , 2011, Nature Cell Biology.

[16]  D. Schindler,et al.  SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype , 2011, Nature Genetics.

[17]  S. West,et al.  Mechanism of Holliday junction resolution by the human GEN1 protein. , 2010, Genes & development.

[18]  N. Shimizu,et al.  Emergence of Micronuclei and Their Effects on the Fate of Cells under Replication Stress , 2010, PloS one.

[19]  S. West,et al.  Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiae. , 2010, DNA repair.

[20]  C. Ponting,et al.  Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. , 2009, Molecular cell.

[21]  J. Yates,et al.  Human SLX4 Is a Holliday Junction Resolvase Subunit that Binds Multiple DNA Repair/Recombination Endonucleases , 2009, Cell.

[22]  Steven P. Gygi,et al.  Mammalian BTBD12/SLX4 Assembles A Holliday Junction Resolvase and Is Required for DNA Repair , 2009, Cell.

[23]  F. Rosselli,et al.  The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities , 2009, Nature Cell Biology.

[24]  I. Hickson,et al.  Replication stress induces sister-chromatid bridging at fragile site loci in mitosis , 2009, Nature Cell Biology.

[25]  S. West,et al.  Identification of Holliday junction resolvases from humans and yeast , 2008, Nature.

[26]  Y. Pommier,et al.  Bloom's syndrome helicase and Mus81 are required to induce transient double-strand DNA breaks in response to DNA replication stress. , 2008, Journal of molecular biology.

[27]  R. Kanaar,et al.  The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks , 2007, Nature Structural &Molecular Biology.

[28]  Kok-Lung Chan,et al.  BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges , 2007, The EMBO journal.

[29]  J. Haber,et al.  Phosphorylation of Slx4 by Mec1 and Tel1 Regulates the Single-Strand Annealing Mode of DNA Repair in Budding Yeast , 2007, Molecular and Cellular Biology.

[30]  Y. Pommier,et al.  Endogenous γ-H2AX-ATM-Chk2 Checkpoint Activation in Bloom's Syndrome Helicase–Deficient Cells Is Related to DNA Replication Arrested Forks , 2007, Molecular Cancer Research.

[31]  Grant W. Brown,et al.  Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4. , 2005, Molecular biology of the cell.

[32]  A. Tong,et al.  A Network of Multi-Tasking Proteins at the DNA Replication Fork Preserves Genome Stability , 2005, PLoS genetics.

[33]  M. Thayer,et al.  Ionizing Radiation Induces Frequent Translocations with Delayed Replication and Condensation , 2004, Cancer Research.

[34]  Simon C Watkins,et al.  Resolution of anaphase bridges in cancer cells , 2004, Chromosoma.

[35]  Ian D. Hickson,et al.  The Bloom's syndrome helicase suppresses crossing over during homologous recombination , 2003, Nature.

[36]  M. Botchan,et al.  Orc mutants arrest in metaphase with abnormally condensed chromosomes. , 2001, Development.

[37]  S Povey,et al.  Dynamic molecular combing: stretching the whole human genome for high-resolution studies. , 1997, Science.

[38]  M. Fenech,et al.  Conversion of excision‐repairable DNA lesions to micronuclei within one cell cycle in human lymphocytes , 1992, Environmental and molecular mutagenesis.

[39]  J V Watson,et al.  A pragmatic approach to the analysis of DNA histograms with a definable G1 peak. , 1987, Cytometry.

[40]  S. Wolff.  Sister chromatid exchange. , 1977, Annual review of genetics.

[41]  J. German,et al.  A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes. , 1974, Proceedings of the National Academy of Sciences of the United States of America.