BIOL 103_Fa.24.11.22_CellCycle - Tagged

Page 1: Overview of Fall 2024 Poster Project

  • Syllabus: Information for rough draft poster due on October 30, worth 5 points.

  • Account Announcements: emphasis on digital poster info, including rating and submission details.

  • Assignments: Key components include selecting gene for poster project due September 27 (2 points), and collaborations within various course modules.

  • Resources: Access to example posters from previous semesters on diseases like Sickle Cell and Cystic Fibrosis, among others.

Page 2: Textbook Readings for November 22

  • Chapter 17.1 - The Eukaryotic Cell Cycle:

    • Phases of the cell cycle, growth factor regulation, and checkpoints significance.

  • Chapter 17.2 - Regulators of Cell Cycle Progression:

    • Mechanisms of growth factor regulation, DNA replication control, and DNA damage checkpoints.

  • Chapter 5.1 - DNA Replication:

    • Proteins/mechanisms at replication forks, mechanisms for accurate replication, and telomerase actions.

  • Upcoming Reading: Chapter 5.2 focuses on DNA repair mechanisms to be discussed on December 2.

Page 3: Introduction to the Cell Cycle

  • The Cell Cycle Overview: All cells reproduce by dividing, ensuring each parental cell gives rise to two daughter cells.

Page 4: Interphase and Mitosis Overview

  • Interphase:

    • Includes G1, S, and G2 phases.

    • Chromosomes decondensed, looking morphologically uniform.

    • Phase Details:

      • G1 Phase: Gap between mitosis and initiation of DNA replication.

      • S Phase: DNA replication occurs.

      • G2 Phase: Continued cell growth, protein synthesis for mitosis, and DNA checking.

Page 5: Mitosis and Cytokinesis

  • Mitosis:

    • Most dramatic stage with daughter chromosome separation.

  • Cytokinesis:

    • Marks the end of mitosis, as cells divide.

Page 6: Clarification on G1 Phase

  • G1 Phase Key Points:

    • Primarily a gap phase, not a direct growth phase.

    • Overall control of progression through the cell cycle.

Page 7: G1 Restriction Point

  • Restriction Point:

    • Controls whether cells enter S phase primarily regulated during G1.

    • Cells may enter G0 phase without growth factors; they remain metabolically active but non-dividing.

Page 8: Embryonic Cell Cycle Characteristics

  • Duration Variation: Different cell types have varying cycle phase durations.

  • Embryonic Mitosis: Lacks a G1 phase, with decreasing cell volume with each cleavage.

Page 9: Yeast Models in Cell Cycle Studies

  • Cell Types Studied:

    • Schizosaccharomyces pombe and Saccharomyces cerevisiae as models for cell cycle research.

Page 10: Stem Cell Division

  • Asymmetric Cell Division in Stem Cells:

    • Produces 2 daughter cells: one self-renewing stem cell and one rapidly dividing transit-amplifying cell.

    • After several divisions, cells differentiate, halting further proliferation.

Page 11: Hematopoietic Stem Cells

  • Source: Blood cells originate from hematopoietic stem cells located in the bone marrow.

  • Production Rate: Approximately 100 billion blood cells are lost per day in humans.

Page 12: Key Principles of the Eukaryotic Cell Cycle

  • Cell Division: All cells reproduce via division, leading to two daughter cells.

  • Symmetric vs. Asymmetric: Division can be equal (symmetric) or unequal (asymmetric).

  • Genome Integrity: Regulation of growth and DNA replication is crucial for maintaining genome integrity.

  • Checkpoints: Prevent transition to the next phase until prior phase events are complete.

Page 13: Main Classes of Regulators in Cell Cycle

  • Classes:

    • Cyclins: Proteins that regulate the cycle.

    • CDKs: Cyclin-dependent kinases.

    • CDCs: Cell division cycle phosphatases.

  • Regulation Points: Important checkpoints at various phases of the cell cycle.

Page 14: Continued Classes of Regulators

  • Regulation Details:

    • G1 has restriction points involving specific cyclin-CDK complexes.

    • Regulation through external signals.

Page 15: Phosphorylation and Cell Cycle Regulation

  • Cdk Activation:

    • Cells are committed to DNA synthesis post-restriction point.

    • Regulation by growth factors in G1 influences cell cycle progression.

Page 16: Growth Factor Pathway Activation

  • Growth Factor Regulation:

    • Activates Ras/Raf/MEK/ERK pathway, stimulating cyclin D synthesis and regulating p27.

Page 17: Rb Protein and E2F

  • Role of Rb:

    • Rb binds E2F transcription factors in G0 and early G1, suppressing cell cycle progression until phosphorylated.

Page 18: Rb Mutations Investigation

  • Questions on the consequences of Rb null mutations and effects of cyclin D silencing on cell division.

Page 19: Reiteration on Growth Factor Regulation in G1

  • Pathway Activation Details:

    • Discusses the Ras/Raf/MEK/ERK pathway and its effects.

Page 20: p27 and Cdk2 Regulation

  • p27 Functions: Inhibits Cdk2/cyclin E during G0 and early G1; involved in cell cycle progression initiation.

Page 21: Cycle Regulatory Components

  • Class Structure: Identifies G1, S, and G2 checkpoint roles through specific cyclin-CDK relationships.

Page 22: Questions on DNA Synthesis and Origins

  • Focused questions regarding DNA synthesis origins and Cdk2/cyclin E activation.

Page 23: Continuation of DNA Synthesis Overview

  • Further elaboration on DNA synthesis origins and regulatory proteins.

Page 24: Eukaryotic Chromosome Replication Initiation

  • Replication Initiation: Occurs at multiple spots along the chromosome, varying between mammalian and yeast cells.

Page 25: Helicase Role in DNA Unwinding

  • Helicase Functionality: Catalyzes unwinding of DNA strands using multimeric enzymes associated with eukaryotic cells.

Page 26: Origin Recognition Complex (ORC)

  • ORC Functions:

    • Guides recruitment of key proteins like MCM and enables phosphorylation for activation.

Page 27: APC/C Functionality

  • Ubiquitin Ligase Role: Interacts with multiple proteins, critical for degradation processes.

Page 28: Recap of APC/C Functions

  • Ubiquitin Explanation: Describes the process and importance of APC/C in cell cycle regulation and protein turnover.

Page 29: DNA Synthesis Queries

  • Questions focusing on replication origins, synthesis activation, and repair mechanisms.

Page 30: DNA Strands Unwinding

d - Single Stranded DNA Binding: Proteins bind and stabilize the unwound strands during replication.

Page 31: Topoisomerase Functions

  • Types of Topoisomerases: Roles of Type I and II in creating reversible breaks and managing DNA supercoiling during replication.

Page 32: DNA Polymerase Accessory Functions

  • Clamp Loading Mechanisms: RFC and PCNA functions in loading the DNA polymerase onto strands for replication.

Page 33: Overview of DNA Polymerases

  • Roles and Types: Different polymerases involved in DNA synthesis and their specific functions in prokaryotic/eukaryotic cells.

Page 34: DNA Polymerase Laws

  • Key Principles: Directions of synthesis, initiation requirements, and differences between DNA and RNA polymerases.

Page 35: Leading and Lagging Strand Dynamics

  • Replication Mechanics: Explains the dosage-dependent and discontinuous replication nature of the lagging strand.

Page 36: RNA Primer Usage

  • Initiation of Replication: Use of short RNA primers synthesized by primase as a crucial component.

Page 37: Lagging Strand Synthesis Methodology

  • Okazaki Fragments: Details on removal of RNA primers and joining of fragments through ligase action.

Page 38: Telomere Structure Overview

  • Telomeres Description: Function and structure of telomeres in eukaryotic chromosomes.

Page 39: Telomerase Functionality

  • Telomerase Role: Describes how reverse transcriptase regulates telomere length during replication.

Page 40: Telomere Activity Maintenance

  • Eukaryotic Specifics: Importance of telomerase for maintaining telomere integrity and its role in cellular aging.

Page 41: Telomere Synthesis Process

  • Detailed Mechanism: Clarifies the telomerase process of extending telomeres and how it interacts with existing strands.

Page 42: Continual Lagging Strand Extension

  • Primer Use During Extension: Importance of primers in forming newly synthesized fragments upon telomere extension.

Page 43: Telomere Length and Cancer Correlation

  • Impact of Telomerase Activity: Discusses implications for somatic cells, cellular aging, and links to cancer proliferation.

Page 44: Summary of DNA Synthesis Topics

  • List of critical questions on synthesis origins and associated mechanisms.

Page 45: Review of Repair Mechanisms

  • Discussed were different DNA repair mechanisms, notably after damage detection and synthesis errors.

Page 46: Fidelity of Replication

  • Importance of Fidelity: Highlights the need for accuracy during DNA replication and its mechanisms.

Page 47: Proofreading Mechanisms of DNA Polymerase

  • Exonuclease Functionality: Role of different polymerases in proofreading newly synthesized DNA strands post-replication.

Page 48: Mismatch Repair System Overview

  • Key Components: MMR's role in identifying and excising mismatched bases to prevent mutations.

Page 49: Review of Repair Mechanisms (Continued)

  • Emphasis on multiple mechanisms for damage repair during DNA synthesis, particularly specialized polymerases.

Page 50: UV Damage Repair Mechanisms

  • Discussed the impact of UV light on DNA and a variety of repair strategies available to the cell.

Page 51: Translesion DNA Synthesis Overview

  • Overview of translesion synthesis in both prokaryotic and eukaryotic cells, indicating specialized polymerase functions.

Page 52: Resumption of Normal Replication

  • Describe the continuum post-translesion synthesis leading back to normal replication mechanics.

Page 53: Recapping Damage and Repair Mechanisms

  • Summary of repair mechanisms and their role during synthesis/governing DNA integrity.

Page 54: DSB Repair Mechanisms

  • Homology-directed Repair and NHEJ: Distinctions between homology-directed repair and non-homologous end joining mechanisms.

Page 55: Non-Homologous End Joining

  • Repair Mechanism Details: Outline of the process for DSB repair through ligase actions and additional nucleases.

Page 56: Overview of HDR and NHEJ

  • Visual Explanation: Diagram representations of the distinct pathways for double-strand break repairs.

Page 57: Understanding Repair Timing

  • Repair Mechanisms: Evaluation of when certain repair mechanisms are essential during the cell cycle.

Page 58: Role of Checkpoints in DNA Damage

  • Key Checkpoint Proteins: Role of ATM and ATR kinases in mediating cell cycle arrest upon DNA damage.

Page 59: ATM and ATR Functions

  • Checkpoint Activation: Mediating DNA repair, cell cycle arrest, and elevating cell apoptosis in response to damage.

Page 60: Cell Cycle Arrest Mechanism Details

  • Inhibition Mechanism: Chk1 and Chk2 mediating cell cycle arrests by inhibiting critical phosphorylation pathways.

Page 61: p53 Regulation in Arrest Mechanisms

  • p53's Role: Functionality of p53 in cell cycle arrest through activation and induction of Cdk inhibitors like p21.