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. 2022 Aug 25;12:949435. doi: 10.3389/fonc.2022.949435

Figure 2.

Figure 2

The ends of the human lineal chromosomes are protected by telomere associated proteins. (A) The lineal nature of the human chromosomes possesses a challenge for integrity maintenance of the human genome. The telomeres at the end of the chromosomes consist of repetitive sequences TTAGGG and their complementary sequence AATCCC. A G-overhang composed by the TTAGGG sequence is the result of incomplete DNA fill-in activity by DNA polymerases at every round of DNA duplication. The G-overhang is bound by RPA1 subunits conferring protection from nucleolytic degradation. (B) Shelterin is telomere protecting complex that is composed by six proteins. TRF1 and TRF2 directly bind the telomeric DNA sequences and recruit other members of the Shelterin complex. Shelterin promotes the t-loop lariat conformation of the G-overhang and inhibits activation of the checkpoint kinases, ATM by TRF2, and ATR by POT1. (C) The telomerase complex is a ribonucleoprotein whose main components are TERT and TERC proteins. TERT synthetizes telomeric DNA using TERT as a template and extends the TTAGGG overhang. (D) The CST complex is composed by the CTC1, STN1, and TEN1. CST complex recruits Pol-a-primase to help fill in the recently extended TTAGGG with the complementary AATCCC. CST complex also inhibits telomerase activity, preventing excessive telomere extension. ATM, ataxia telangiectasia mutated; ATR, ATM and Rad3 related; CTC1, conserved telomere protection component 1; POT1, protection of telomeres 1; RPA1, Replication Protein A1; STN1, suppressor of cdc thirteen 1; TEN1, telomeric pathway with STN1; TERC, telomerase RNA template component; TERRA, telomeric repeat-containing RNA; TERT, telomerase reverse transcriptase; TRF1, telomeric repeat binding factor 1; TRF2, telomeric repeat binding factor 2.