Localization-dependent and -independent roles of SLX4 in regulating telomeres

2015-01-13

Localization-dependent and -independent roles of SLX4 in regulating telomeres


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Abstract
SLX4, a scaffold for structure-specific DNA repair nucleases, is important for several types of DNA repair. Many repair proteins bind to sites of DNA damage, resulting in subnuclear "foci," but SLX4 forms foci in human cells even without DNA damage. Using several approaches, we show that most, but not all, SLX4 foci localize to telomeres in a range of human cell lines irrespective of the mechanisms used to maintain telomere length. The SLX1 Holliday-junction-processing enzyme is recruited to telomeres by SLX4, and SLX4, in turn, is recruited by a motif that binds to the shelterin subunit TRF2 directly. We also show that TRF2-dependent recruitment of SLX4 prevents telomere damage. Furthermore, SLX4 prevents telomere lengthening and fragility in a manner that appears to be independent of telomere association. These findings reveal that SLX4 plays multiple roles in regulating telomere homeostasis.

Some notes
Mechanisms of Telomere Length Maintenance
Human Cells
SLX4 in Promoting Telomere Homeostasis
From this perspective, SLX4 might mediate ‘‘telo-
mere trimming,’’ a mechanism that has been proposed to pre-
vent overlengthening of telomeres
The consequences of overlong telomeres
for cell function and organism function are not clear, but this
will be interesting to study.
Independently of TRF2