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Introduction
increasing the interaction between homologous and heterologous
chromosomes [173].
Unlike yeast, telomeres of mammalian cells are randomly positioned
throughout the nucleus [174]. In telomerase negative cancer cells, telomeres
are highly mobile and can associate with each other. SUMOylation of yeast
telomeric proteins leads to anchoring of telomeres at nuclear envelope,
whereas SUMOylation of mammalian telomeric proteins triggers the
formation of promyelocytic leukemia (PML) bodies around the telomeres.
These PML body will be later enriched with repair and recombination factors
and undergo ALT mediated telomere lengthening followed by disassembly of
the PML body and release of the telomeres [175].
Figure 11: Slowly repaired or persistent DSB are recruited to nuclear envelop. The
recruitment serves to decide if the DSB can be repaired by canonical HR or alternative
methods like de novo telomere healing. Nuclear pore-associated Slx5/Slx8 ubiquitylates
and directs the associated proteins at break site to proteosome mediated degradation to
mediate efficient repair (Source: [176]).
In yeast, Irrepairable DSB and collapsed replication forks are also localized to
the nuclear envelope in a Mec1/Tel1-dependent manner (See figure 11).
Nuclear pore-associated Slx5/Slx8 ubiquitylates and degrades the protein
associated at break site to mediate efficient repair.
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