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Intro; Supervisor's Foreword; Abstract; Preface; Acknowledgements; Contents; List of Contributors; Acronyms and Abbreviations; List of Figures; List of Tables; 1 Introduction; 1.1 Premature Aging and Genomic Instability; 1.1.1 Chronological Aging and Premature Aging; 1.1.2 A Brief Background of Progeroid Syndromes; 1.1.3 Genomic Instability and Premature Aging; 1.2 Lamins and Laminopathies; 1.2.1 The Nuclear Lamins; 1.2.2 A Brief Outlook of Laminopathies; 1.2.3 Hutchinson-Gilford Progeria Syndrome (HGPS); 1.2.4 Atypical HGPS Conditions; 1.3 Role of Sirtuins in Premature Aging
1.3.1 Sirtuins … At a Glance1.3.2 Sirt1; 1.3.3 Sirt2; 1.3.4 Sirt3; 1.3.5 Sirt4; 1.3.6 Sirt5; 1.3.7 Sirt6; 1.3.8 Sirt7; 1.4 An Overview of SIRT6; 1.4.1 Structure and Localization of SIRT6; 1.4.2 Diverse Functions of SIRT6; 1.4.3 Post-translational Modifications of SIRT6; 1.4.4 Perspectives; 1.5 p53: In a Nutshell; 1.5.1 Domains of p53 and Their Associated Functions; 1.5.2 Mechanisms of p53 Activation and Regulation; 1.5.3 Perspectives; 1.6 Hypotheses and Objectives of Study; 1.6.1 Hypothesis I: A Potential Interlinkage Between Lamins and SIRT6 in DNA Damage Repair and Premature Aging
1.6.2 Hypothesis II: A Potential Functional Interlinkage Between SIRT6 and P53 in Accelerated Cellular Senescence and Premature Aging1.6.3 Hypothesis III: Other Post-translational Modifications of SIRT6 with Regulatory Roles in DNA Damage Repair Process; References; 2 Materials and Methods; 2.1 Materials; 2.1.1 Cell Lines; 2.1.2 Mouse Lines; 2.1.3 Constructs; 2.1.4 Antibodies; 2.1.5 Reagents; 2.1.6 Primers; 2.2 Methods; 2.2.1 Cell Culture, Transfections and Treatment with Reagents; 2.2.2 Mouse Embryonic Fibroblast (MEF) Collection; 2.2.3 Genotyping of Tissues from Mice
2.2.18 Isolation of Bone Marrow Stromal Cells, and Cells from Thymus and Spleen2.2.19 Immunostaining for Fluorescence-Activated Cell Sorting (FACS) Analysis; 2.2.20 Annexin-V Staining; 2.2.21 Statistical Analysis; References; 3 Results-I. Lamin A is an Endogenous Activator of SIRT6 in DNA Damage Repair Process; 3.1 Introduction; 3.2 Results; 3.2.1 Lamin A is a Direct Interacting Partner of SIRT6; 3.2.2 The Core Domain of SIRT6 Plays a Critical Role in Interacting with Lamin A; 3.2.3 The C-Terminus of Lamin A Dictates Its Binding with SIRT6; 3.2.4 Lamin A Enhances SIRT6 Deacetylase Activity
1.3.1 Sirtuins … At a Glance1.3.2 Sirt1; 1.3.3 Sirt2; 1.3.4 Sirt3; 1.3.5 Sirt4; 1.3.6 Sirt5; 1.3.7 Sirt6; 1.3.8 Sirt7; 1.4 An Overview of SIRT6; 1.4.1 Structure and Localization of SIRT6; 1.4.2 Diverse Functions of SIRT6; 1.4.3 Post-translational Modifications of SIRT6; 1.4.4 Perspectives; 1.5 p53: In a Nutshell; 1.5.1 Domains of p53 and Their Associated Functions; 1.5.2 Mechanisms of p53 Activation and Regulation; 1.5.3 Perspectives; 1.6 Hypotheses and Objectives of Study; 1.6.1 Hypothesis I: A Potential Interlinkage Between Lamins and SIRT6 in DNA Damage Repair and Premature Aging
1.6.2 Hypothesis II: A Potential Functional Interlinkage Between SIRT6 and P53 in Accelerated Cellular Senescence and Premature Aging1.6.3 Hypothesis III: Other Post-translational Modifications of SIRT6 with Regulatory Roles in DNA Damage Repair Process; References; 2 Materials and Methods; 2.1 Materials; 2.1.1 Cell Lines; 2.1.2 Mouse Lines; 2.1.3 Constructs; 2.1.4 Antibodies; 2.1.5 Reagents; 2.1.6 Primers; 2.2 Methods; 2.2.1 Cell Culture, Transfections and Treatment with Reagents; 2.2.2 Mouse Embryonic Fibroblast (MEF) Collection; 2.2.3 Genotyping of Tissues from Mice
2.2.18 Isolation of Bone Marrow Stromal Cells, and Cells from Thymus and Spleen2.2.19 Immunostaining for Fluorescence-Activated Cell Sorting (FACS) Analysis; 2.2.20 Annexin-V Staining; 2.2.21 Statistical Analysis; References; 3 Results-I. Lamin A is an Endogenous Activator of SIRT6 in DNA Damage Repair Process; 3.1 Introduction; 3.2 Results; 3.2.1 Lamin A is a Direct Interacting Partner of SIRT6; 3.2.2 The Core Domain of SIRT6 Plays a Critical Role in Interacting with Lamin A; 3.2.3 The C-Terminus of Lamin A Dictates Its Binding with SIRT6; 3.2.4 Lamin A Enhances SIRT6 Deacetylase Activity