week 2 lecture 2: cell reproduction, senescence and death 2

• what is replicative senescence?

  the process by which normal somatic cells reach an irreversible stage of cell cycle arrest following multiple rounds of replication
• what is replicative senescence associated with?

  marked changes in gene expression and function
• telomere shortening occurs with cell division and limits replicative capacity of cells (replicative senescence)
• senescent cells accumulate with age and in age-related diseases
• what are senescent cells associated with?

  loss of tissue function with aging
• what is telomerase?

  the enzyme responsible for the maintenance of the length of telomeres by addition of guanine-rich repetitive sequences
• where is telomerase activity exhibited?

  in gametes, and stem and tumor cells
• what are the 2 types of cell death?

  1. necrosis
  2. apoptosis
• In the 1960’s, what did Leonard Hayflick and his colleagues demonstrate?

  when normal (somatic) human cells are grown in culture, they lose their ability to divide after a limited number of cell divisions
• what did Leonard Hayflick also discover about fibroblasts (and other normal human cells) derived from foetal, embryonic, and/or newborn tissue?

  it can undergo between 40 and 60 cell divisions, but then cannot divide anymore
• what is the hayflick limit?

  the cellular dividing limit before entering senescence (40-60)
• what is stress-induced premature senescence?

  when environmental stress hastens the shrivelling of the tips of telomeres, alters the phenotypic characteristics, and accelerates the process of senescence
• how does ROS contribute to stress-induced premature senescence?

  oxidative stress occurs due to excessive amounts of reactive oxygen species (ROS), which damages macromolecules and helps drive stress-induced premature senescence
• what is an oncogene known as before becoming mutated?

  a proto-oncogene (a gene involved in normal cell growth and division)
• what is oncogene-induced senescence?

  a fail-safe mechanism that suppresses cell proliferation caused by incorrect activation of oncoproteins in normal cells
• what is pleiotropy?

  when a single gene affects two or more characters
• what is antagonist pleiotropy?

  when a gene has multiple effects; one effect is beneficial for an organism's fitness, while another effect is detrimental
• what is replicative stress-induced senescence?

  when cells undergo irreversible growth arrest, due to persistent DNA damage or other forms of cellular stress incurred during DNA replication
• replicative (stress-induced) senescence accounts for early DNA damage
• replication stress causes the functional decline of ageing haematopoietic stem cells
• what is developmental senescence?

  a form of programmed senescence that contributes to morphogenesis, during embryonic development
• what is morphogenesis?

  the process that causes a cell, tissue or organism to develop its shape
• what is cell-cell fusion?

  when two cells combine their plasma membranes and become a single cell, and retain certain genetic information from each parent cell
• what is the syncytiotrophoblast (ST)?

  the placental barrier between maternal and foetal blood, that allows nutrient and gas exchanges
• what does the syncytiotrophoblast represent in the human placenta?

  the endocrine tissue
• what is the chromosome capping function?

  a function that protects the telomere against homologous recombination and non-homologous end joining (chromosomal instability)
• what is homologous recombination?

  a type of genetic recombination where nucleotide sequences are exchanged between two similar/identical molecules of DNA
• what is non-homologous end joining?

  when DNA ends are paired in a multi-protein synaptic complex to promote their direct ligation
• chromosome capping function prevents the ends of chromosomes from being "seen" as double-stranded breaks
• what is the shelterin complex?

  a multiprotein complex that plays central roles in telomere biology; mutations of it are associated with premature aging diseases and cancer
• telomeres are DNA-protein complexes that cap the ends of linear chromosomes
• what are telomeres important for the regulation of?

  replicative senescence and maintaining genome stability
• which part of the telomere is vital for its function?

  the G-rich, single-stranded (ss) 3' overhang
• what does the structure of a telomere consist of?

  G-rich repetitive sequences that end in a 3' single-strand overhang
• the G-strand overhang loops back to form a T-loop and invades the 5' double-stranded telomeric duplex, forming a D-loop
• dna polymerases cannot lengthen the terminal section of lagging strand (primer site)
• how long is the terminal section?

  approximately 100-200 bp (basepairs)
• what is the primer site?

  where DNA replication begins
• what affect does p21 induction have?

  it causes cell cycle arrest in senescent cells
• what is the end replication problem?

  the idea that the ends of linear DNA cannot be replicated completely during lagging strand DNA synthesis