Catastrophic chromosomal restructuring during genome elimination in plants

  1. Ek Han Tan
  2. Isabelle M Henry
  3. Maruthachalam Ravi
  4. Keith R Bradnam
  5. Terezie Mandakova
  6. Mohan P A Marimuthu
  7. Ian Korf
  8. Martin A Lysak
  9. Luca Comai  Is a corresponding author
  10. Simon W L Chan
  1. University of California, Davis, United States
  2. Indian Institute of Science Education and Research, India
  3. Masaryk University, Czech Republic

Abstract

Genome instability is associated with mitotic errors and cancer. This phenomenon can lead to deleterious rearrangements, but also genetic novelty, and many questions regarding its genesis, fate and evolutionary role remain unanswered. Here, we describe extreme chromosomal restructuring during genome elimination, a process resulting from hybridization of Arabidopsis plants expressing different centromere histones H3. Shattered chromosomes are formed from the genome of the haploid inducer, consistent with genomic catastrophes affecting a single, laggard chromosome compartmentalized within a micronucleus. Analysis of breakpoint junctions implicates breaks followed by repair through non-homologous end joining (NHEJ) or stalled fork repair. Furthermore, mutation of required NHEJ factor DNA Ligase 4 results in enhanced haploid recovery. Lastly, heritability and stability of a rearranged chromosome suggest a potential for enduring genomic novelty. These findings provide a tractable, natural system towards investigating the causes and mechanisms of complex genomic rearrangements similar to those associated with several human disorders.

Article and author information

Author details

  1. Ek Han Tan

    Department of Plant Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Isabelle M Henry

    Department of Plant Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maruthachalam Ravi

    School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Keith R Bradnam

    Genome Center, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Terezie Mandakova

    Central European Institute of Technology, Masaryk University, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  6. Mohan P A Marimuthu

    Department of Plant Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Ian Korf

    Genome Center, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Martin A Lysak

    Central European Institute of Technology, Masaryk University, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  9. Luca Comai

    Department of Plant Biology, University of California, Davis, Davis, United States
    For correspondence
    lcomai@ucdavis.edu
    Competing interests
    The authors declare that no competing interests exist.
  10. Simon W L Chan

    Department of Plant Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Bernard de Massy, Institute of Human Genetics, CNRS UPR 1142, France

Publication history

  1. Received: January 16, 2015
  2. Accepted: May 14, 2015
  3. Accepted Manuscript published: May 15, 2015 (version 1)
  4. Version of Record published: June 10, 2015 (version 2)
  5. Version of Record updated: April 19, 2017 (version 3)

Copyright

© 2015, Tan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 5,112
    Page views
  • 1,147
    Downloads
  • 69
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Ek Han Tan
  2. Isabelle M Henry
  3. Maruthachalam Ravi
  4. Keith R Bradnam
  5. Terezie Mandakova
  6. Mohan P A Marimuthu
  7. Ian Korf
  8. Martin A Lysak
  9. Luca Comai
  10. Simon W L Chan
(2015)
Catastrophic chromosomal restructuring during genome elimination in plants
eLife 4:e06516.
https://doi.org/10.7554/eLife.06516
  1. Further reading

Further reading

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Meng Huang, Minjie Hong ... Xuezhu Feng
    Research Article Updated

    Histone methylation plays crucial roles in the development, gene regulation, and maintenance of stem cell pluripotency in mammals. Recent work shows that histone methylation is associated with aging, yet the underlying mechanism remains unclear. In this work, we identified a class of putative histone 3 lysine 9 mono/dimethyltransferase genes (met-2, set-6, set-19, set-20, set-21, set-32, and set-33), mutations in which induce synergistic lifespan extension in the long-lived DAF-2 (insulin growth factor 1 [IGF-1] receptor) mutant in Caenorhabditis elegans. These putative histone methyltransferase plus daf-2 double mutants not only exhibited an average lifespan nearly three times that of wild-type animals and a maximal lifespan of approximately 100 days, but also significantly increased resistance to oxidative and heat stress. Synergistic lifespan extension depends on the transcription factor DAF-16 (FOXO). mRNA-seq experiments revealed that the mRNA levels of DAF-16 Class I genes, which are activated by DAF-16, were further elevated in the daf-2;set double mutants. Among these genes, tts-1, F35E8.7, ins-35, nhr-62, sod-3, asm-2, and Y39G8B.7 are required for the lifespan extension of the daf-2;set-21 double mutant. In addition, treating daf-2 animals with the H3K9me1/2 methyltransferase G9a inhibitor also extends lifespan and increases stress resistance. Therefore, investigation of DAF-2 and H3K9me1/2 deficiency-mediated synergistic longevity will contribute to a better understanding of the molecular mechanisms of aging and therapeutic applications.

    1. Chromosomes and Gene Expression
    2. Structural Biology and Molecular Biophysics
    Lena Maria Muckenfuss, Anabel Carmen Migenda Herranz ... Martin Jinek
    Research Article Updated

    3′ end formation of most eukaryotic mRNAs is dependent on the assembly of a ~1.5 MDa multiprotein complex, that catalyzes the coupled reaction of pre-mRNA cleavage and polyadenylation. In mammals, the cleavage and polyadenylation specificity factor (CPSF) constitutes the core of the 3′ end processing machinery onto which the remaining factors, including cleavage stimulation factor (CstF) and poly(A) polymerase (PAP), assemble. These interactions are mediated by Fip1, a CPSF subunit characterized by high degree of intrinsic disorder. Here, we report two crystal structures revealing the interactions of human Fip1 (hFip1) with CPSF30 and CstF77. We demonstrate that CPSF contains two copies of hFip1, each binding to the zinc finger (ZF) domains 4 and 5 of CPSF30. Using polyadenylation assays we show that the two hFip1 copies are functionally redundant in recruiting one copy of PAP, thereby increasing the processivity of RNA polyadenylation. We further show that the interaction between hFip1 and CstF77 is mediated via a short motif in the N-terminal ‘acidic’ region of hFip1. In turn, CstF77 competitively inhibits CPSF-dependent PAP recruitment and 3′ polyadenylation. Taken together, these results provide a structural basis for the multivalent scaffolding and regulatory functions of hFip1 in 3′ end processing.