Nuclear Pore Complexes in Genome Organization, Function and Maintenance

Maximiliano D'Angelo, Ph.D., is Faculty of the Development, Aging and Regeneration Program and the Immunity and Pathogenesis Program at the Sanford Burnham Medical Discovery Institute in La Jolla, California. He is also member of the Tumor Initiation and Maintenance Program of the NCI-designated Cancer Center. Before moving to SBP, Dr. D'Angelo was a Principal investigator of the Cardiovascular Research Institute at the University of California San Francisco and Assistant Professor of the Department of Biochemistry & Biophysics. Dr. D'Angelo received his Ph.D. in molecular biology from the University of Buenos Aires, Argentina, and trained at The Scripps Research Institute and the Salk Institute for Biological before beginning his independent career. He has been Fellow of the Ellison Foundation and American Federation for Aging Research, Pew Latin American Fellow, Pew Biomedical Scholar and Scholar of the American Cancer Society.

lt;b>Nuclear Pore Complexes In The Regulation Of Genome Organization And Gene Expression

Contents:

1. Spatial Organization Of The Nucleus Compartmentalizes And Regulates The Genome

1.1 Introduction

1.2 Subdomains of the nucleus

1.2.2 Nuclear pore complexes

1.2.3 Chromosomes

1.2.5 Telomeres

1.2.6 Nucleolus

1.2.8 Cajal bodies

1.2.9 Gemini of coiled bodies

1.2.11 Speckles

1.2.12 Paraspeckles

1.2.14 Polycomb bodies

1.3 Composition of nuclear structures

1.5 Genome organization patterns

1.5.1 Loops and topologically-associated domains

1.5.2 Compartments

1.6 Structure-function relationships

1.6.1 Layers of functional separation

1.6.2 Loops

1.6.3 Scaffolds

1.6.4 Boundary elements

1.7 General versus tissue- or state-specific functions

1.8 Conclusions and open questions

1.9 References

2. The Molecular Composition And Function Of The Nuclear Periphery And Its Impact On The Genome

C. Patrick Lusk and Megan C. King

2.1 The conservation of the spatial positioning of the genome across eukaryotes

2.2 Integral INM proteins

2.3 A brief history of INM targeting

2.4 The nuclear lamina

2.5 Lamina Associated Domains

2.6 LADs as developmentally regulated regions

2.7 Histone modifications at the nuclear periphery

2.8 Peripheral tethers

2.9 Lamina Associated Sequences

2.10 Beyond silencing: the periphery and genome integrity

2.11 Repetitive DNA and the nuclear periphery

2.12 Inputs of nuclear compartmentalization on DNA repair mechanisms

2.13 Outlook

2.14 References

3. Nuclear Pore Complexes: Fascinating Nucleocytoplasmic Checkpoints

Victor Shahin

3.1 Introduction

3.2 Versatility of the NPCs structural configuration

3.3 Composition, heterogeneity and dynamics of the NPCs

3.4 NPCs as fascinating gatekeepers between the cytoplasm and the nucleus

3.5 Configuration and functional mechanisms of the selective NPC barrier: FG-Nups

3.6 References

4. Nuclear Pore Complex In Genome Organization And Gene Expression In Yeast

Carlo Randise-Hinchliff and Jason H Brickner

4.1 Introduction

4.2 Spatial organization of the yeast genome

4.4 Nuclear pore complex interacts with the genome

4.5 Nups influence transcription

4.7 Interchromosomal clustering at the NPC

4.8 Regulation of gene recruitment and clustering

4.9 Gene recruitment and clustering through the cell cycle

4.10 Transcription Memory

4.11 Molecular mechanism of INO1 transcriptional memory

4.12 Concluding Remarks

4.13 References

5. Nuclear Pore Complex In Genome Organization And Gene Expression In Drosophila

Terra Kuhn and Maya Capelson

5.1 Introduction

5.2 Unique features of Drosophila NPC structure and assembly

5.3 Phenotypes of Drosophila Nups

5.3.1 Components of the Nup107-160 sub-complex in Drosophila speciation

5.3.2 NPC components and ALS/FTD pathogenesis

5.3.3 Cytoplasmic Nups in immune response and import of NF- B

5.3.4 Roles of Drosophila Nups in germ cell development

5.4 Chromatin-binding roles of Drosophila Nups in gene regulation

5.4.1 Nups interact with chromatin on and off the NPC

5.4.2 Drosophila Nups and Dosage Compensation machinery

5.4.3 Physiological gene targets of Drosophila Nups

5.4.4 Roles of Drosophila Nups in non-transcribing chromatin

5.4.5 Possible mechanisms of gene regulatory roles of Nups

5.5 Concluding Remarks

5.6 References

6. Caenorhabditis elegans Nuclear Pore Complexes In Genome Organization And Gene Expression

Celia María Muñoz-Jiménez and Peter Askjaer

6.2 C. elegans NPC composition

6.3 Association of nups with chromatin

6.5 The NPC in nucleocytoplasmic transport and beyond

6.6 The NPC during aging

6.8 References

7. Mammalian Nuclear Pore Complexes In Genome Organization And Gene Expression

Marcela Raices and Maximiliano A D'Angelo

7.2 Stability, mobility and lifespan of mammalian NPCs

7.3 Chromatin interactions with mammalian NPCs

7.4 Gene expression regulation at NPCs

7.4.1 Genes that associate with mammalian NPCs

7.4.2 Mechanisms of gene-expression regulation by NPCs

7.5 Gene expression regulation by nucleoporins in the nuclear interior

7.5.1 Genes that associate with intranuclear nucleoporins

7.5.2 Mechanisms of gene-expression regulation by intranuclear nucleoporins

7.6 Gene regulation by abnormal nucleoporin fusion proteins

7.7 Concluding Remarks

7.8 References

8. Nuclear Pore Complexes, Genome Organization And HIV-1 Infection

Francesca Di Nunzio

8.1 Introduction

8.2 Early steps of HIV-1 infection

8.3 Role of NPC Components in HIV-1 Replication

8.3.1 Nups and HIV-1 Uncoating

8.3.2 Nups and HIV-1 Translocation

8.3.3 Nups and HIV-1 Integration

8.4 Concluding Remarks

8.5 References

9. Nuclear Pore Complexes In DNA Repair And Telomere Maintenance

9.1 The Nuclear Pore Complex: overall organization and architectural plasticity

9.2 NPC and DNA repair in yeast

9.2.1 Role of Nucleoporins

9.2.2 NPC regulates HR at specific types of DNA lesions

9.3 NPC and DNA repair in mammals

9.4 NPC regulates telomere recombination during pre-senescence and survivor formation

9.5 Concluding Remarks

9.6 References

10. NPCs in mitosis and chromosome segregation Masaharu Hazawa, Akiko Kobayashi and Richard W. Wong

10.1 NPC structure and composition

10.2 Function of NPC components in chromosome segregation and mitotic apparatus orchestration during mitosis

10.2.1 Nup358/RanBP2 subcomplex in mitosis

10.2.2 Nup62 subcomplex in mitosis

10.2.4 Tpr-Nup153 subcomplex in mitosis

10.2.5 Rae1-Nup98 subcomplex in mitosis

10.4 ESCRT-III in NE/NPC sealing at the end of mitosis

10.5 Concluding Remarks

10.6 References