Figure 1.

DNA damage response at telomeres and chromosome sites in somatic cells and cancer cells  (A) Telomeric DNA damage response in normal cells. Cells consistently lose telomeres with each replication cycle and/or with the exposure to endogenous and exogenous DNA damages. Upon DNA damage, repair proteins are recruited to damaged telomeres, which also serve as signals for the activation of the cell cycle checkpoint mechanism rather than initiation of impropriate repair leading to chromosomal fusions. The persistent cell cycle arrest transits the cells into senescence. The deficiencies of p53 or Rb genes antagonize cell cycle arrest, leading to cell death or cancerous transformation. Cells that undergo ‘telomere crisis’ exhibit short telomeres or chromosomal fusions. (B) DNA damage response at non-telomeric regions. A subsequent DNA repair pathways including base-excision repair (BER), single-strand break repair (SSBR), HR, and NHEJ and the sequential DNA damage signal cascade are activated at sites of DNA damage. (C) Telomere maintenance in cancer cells. About 80% cancer cells express telomerase and 15% cancer cells use ALT pathway for telomere maintenance. Telomerase catalyzes the elongation of the telomeres and inhibits the DNA damage signals. Cancer cells utilize ALT pathway to prevent telomere shortening characterized by heterogeneous telomere lengths. ALT cancer cells are resistant to NHEJ in response to telomeric DNA damage, but show frequent recruitments of HR proteins at telomeres.