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. 2023 Nov 27;24(23):16830. doi: 10.3390/ijms242316830

Figure 4.

Figure 4

TRF1 and TRF2 promote proper telomere localization in APBs and telomere replication in ALT cells. (a) Two proposed models for how shelterin SUMOylation by MMS21 helps telomeres stay in APBs. In the recruitment model, MMS21 induces the SUMOylation of the shelterin complex within the nucleoplasm, leading to the subsequent attraction of telomeres to PML bodies for recombination and elongation. In the maintenance model, MMS21 is present in APBs independently of telomeres. When telomeres are brought to APBs, shelterin is SUMOylated by MMS21, which facilitates telomere recombination. (b) The SUMOylation of TRF2 mediated by PIAS4 and MMS21 enhances the recruitment of DDR-related proteins to APBs and facilitates break-induced replication (BIR). (c) In G1 phase, TRF2 binds to MUS81 and suppresses its nuclease activity within APBs. In G2 phase, TRF2 releases MUS81 in the APBs which activates MUS81 to cleave the recombination intermediates.