Rap1 Affects the Length and Heterogeneity of Human Telomeres
AUTOR(ES)
Li, Bibo
FONTE
The American Society for Cell Biology
RESUMO
Telomere length is controlled in part by cis-acting negative regulators that limit telomere extension by telomerase. In budding yeast, the major telomere length regulator scRap1 binds to telomeric DNA and acts to inhibit telomere elongation in cis. Because the human Rap1 ortholog hRap1 does not bind to telomeric DNA directly but is recruited to telomeres by TRF2, we examined its role in telomere length control. The data are consistent with hRap1 being a negative regulator of telomere length, indicating functional conservation. Deletion mapping confirmed that hRap1 is tethered to telomeres through interaction of its C terminus with TRF2. The telomere length phenotypes of hRap1 deletion mutants implicated both the BRCT and Myb domain as protein interaction domains involved in telomere length regulation. By contrast, scRap1 binds to telomeres with its Myb domains and uses its C terminus to recruit the telomere length regulators Rif1 and Rif2. Together, our data show that although the role of Rap1 at telomeres has been largely conserved, the domains of Rap1 have undergone extensive functional changes during eukaryotic evolution. Surprisingly, hRap1 alleles lacking the BRCT domain diminished the heterogeneity of human telomeres, indicating that hRap1 also plays a role in the regulation of telomere length distribution.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=284807Documentos Relacionados
- Human RAP1 inhibits non-homologous end joining at telomeres
- Sequential Regulation of the Small GTPase Rap1 in Human Platelets
- Mechanism of the spatio-temporal regulation of Ras and Rap1
- RAP1 controls rhoptry targeting of RAP2 in the malaria parasite Plasmodium falciparum
- Characterisation of the DNA binding domain of the yeast RAP1 protein.