Cell Senescence, Telomeres, and Chromosomal Instability in Cancer

What are primary cells?

Cells taken from living tissue and grown in culture for the first time with finite lifespans.

What is senescence?

A permanent growth arrest state where cells remain metabolically active but can no longer divide.

What causes senescence?

Telomere shortening, DNA damage, oxidative stress, or activation of p53/pRB pathways.

What are dicentric chromosomes?

Chromosomes with two centromeres formed when broken chromosome ends lacking telomeres fuse together.

What is the problem with dicentric chromosomes during cell division?

They are pulled toward opposite poles, causing chromosome breakage and genomic instability.

What are breakage-fusion-bridge cycles?

A cycle of chromosomal instability that occurs when telomeres are lost or damaged.

What happens during breakage-fusion-bridge cycles?

Chromosomes break, fuse to form dicentric chromosomes, and break again during anaphase.

What are internuclear bridges?

Strands of chromatin that connect two daughter nuclei after mitosis when dicentric chromosomes fail to separate.

What are telomeres?

Specialized DNA-protein complexes at the end of chromosomes that protect them from degradation.

What happens to telomeres with each cell division?

They shorten, leading to senescence when they become critically short.

What is the Hayflick limit?

The maximum number of times a normal human cell population can divide before entering senescence.

What triggers senescence?

Telomere shortening, DNA damage, oncogenic stress, and activation of tumor suppressor pathways.

What are the appearance and molecular characteristics of senescent human fibroblasts?

Enlarged, flat, vacuolated appearance; permanent G1 arrest; active p53 and pRB pathways; high B-galactosidase activity; shortened telomeres.

What is the structure of human telomeres?

Repeated DNA sequences and protective proteins that fold back to form a T-loop.

What is the repeated sequence in human telomeres?

TTAGGG repeated thousands of times.

What is telomerase?

A ribonucleoprotein enzyme that extends telomeres.

What are the main components of human telomerase?

hTERT (catalytic protein) and hTR (RNA component), along with about 8 accessory proteins.

What are the mechanisms by which cancer cells overcome telomere shortening?

Telomerase activation (85-90% of tumors) and ALT (Alternative Lengthening of Telomeres, 10-15% of tumors).

What steps are necessary for a cell to become immortal?

Bypass senescence, bypass crisis, accumulate mutations, and gain oncogenic signaling.

What is the difference between cellular senescence and crisis?

Senescence is a permanent growth arrest due to telomere shortening; crisis involves severe telomere loss and genomic instability.

Do senescent cells promote or suppress cancer?

Both; they suppress early tumorigenesis but can promote late-stage cancer through inflammatory factors.