BBH 210 Telomeres Lectures 1-3

Hermann Muller

coined the term telomere

• found that a chromosome cannot persist indefinitely without having its ends sealed

end replication problem

each round of DNA replication leaves 12-30 DNA unreplicated

• telomeres progressively shorten in all human cells that divide

• proposed by Olovnikov

shelterin

protein complex in telomeres

• concentration increases in the nucleus as telomeres shorten, increasing the likelihood of telomeric binding

  • consequence of telomere shortening

telomere position effect (TPE)

telomeres can influence genes over long distances

• gene X will be active when telomeres shorten to reveal the gene

hayflick limit

the telomere provides a means for counting cell division

• there is a limit in cell division

telomerase

enzyme with RNA and protein components

• adds telomeric repeat directly to the DNA sequence

• expressed by almost all cancer cells

  • not expressed by somatic cells

consequences of short telomeres

loss of tissue renewal capacity

failure of stem cells to divide in sufficient numbers

SASP

increase cancer risk

cardiovascular disease

senescence associated secretory phenotype (SASP)

consequence of short telomeres

• causes inflammation and decreased immune response

HeLa cells

cell line derived from cervical cancer cells from Henrietta Lacks

• proliferate abnormally rapidly

• have active version of telomerase

• circumvent the Hayflick limit

Dr. Hans Selye’s definition of stress

that which accelerates the rate of aging through the wear and tear of daily living

types of adverse childhood experiences (ACEs)

abuse

neglect

household dysfunction