Post-translational modifications of TRF1 and TRF2 and their roles in telomere maintenance.
Telomeres, heterochromatic structures, found at the ends of linear eukaryotic chromosomes, function to protect natural chromosome ends from nucleolytic attack. Human telomeric DNA is bound by a telomere-specific six-subunit protein complex, termed shelterin/telosome. The shelterin subunits TRF1 and TRF2 bind in a sequence-specific manner to double-stranded telomeric DNA, providing a vital platform for recruitment of additional shelterin proteins as well as non-shelterin factors crucial for the maintenance of telomere length and structure. Both TRF1 and TRF2 are engaged in multiple roles at telomeres including telomere protection, telomere replication, sister telomere resolution and telomere length maintenance. Regulation of TRF1 and TRF2 in these various processes is controlled by post-translational modifications, at times in a cell-cycle-dependent manner, affecting key functions such as DNA binding, dimerization, localization, degradation and interactions with other proteins. Here we review the post-translational modifications of TRF1 and TRF2 and discuss the mechanisms by which these modifications contribute to the function of these two proteins.
Department of Biology, LSB438, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
John R
JR
Walker
Xu-Dong
XD
Zhu
D000818:Animals; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology; D051381:Rats; D058207:Sumoylation / Q000502:physiology; D059505:Telomere Homeostasis; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D011484:Protein-Arginine N-Methyltransferases