Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends

Abstract Telomere DNA ends with a single-stranded 3′ overhang. Long 3′ overhangs may cause aberrant DNA damage responses and accelerate telomere attrition, which is associated with cancer and aging, respectively. Genetic studies have indicated several important players in preventing 5′ end hyper-res...

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Autores principales:	Rikard Runnberg, Saishyam Narayanan, Marita Cohn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ea94b149eb7b4623a8c3eeb2d766981c
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spelling	oai:doaj.org-article:ea94b149eb7b4623a8c3eeb2d766981c2021-12-02T15:04:59ZRap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends10.1038/s41598-017-08663-x2045-2322https://doaj.org/article/ea94b149eb7b4623a8c3eeb2d766981c2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08663-xhttps://doaj.org/toc/2045-2322Abstract Telomere DNA ends with a single-stranded 3′ overhang. Long 3′ overhangs may cause aberrant DNA damage responses and accelerate telomere attrition, which is associated with cancer and aging, respectively. Genetic studies have indicated several important players in preventing 5′ end hyper-resection, yet detailed knowledge about the molecular mechanism in which they act is still lacking. Here, we use an in vitro DNA 5′ end protection assay, to study how N. castellii Cdc13 and Rap1 protect against 5′ exonucleolytic degradation by λ-exonuclease. The homogeneous telomeric repeat sequence of N. castellii allows us to study their protection ability at exact binding sites relative to the 5′ end. We find efficient protection by both Cdc13 and Rap1 when bound close to the 5′ end. Notably, Rap1 provides protection when binding dsDNA at a distance from the 5′ end. The DNA binding domain of Rap1 is sufficient for 5′ end protection, and its wrapping loop region is essential. Intriguingly, Rap1 facilitates protection also when its binding site contains 2 nt of ssDNA, thus spanning across the ds-ss junction. These results highlight a role of Rap1 in 5′ end protection and indicate that Cdc13 and Rap1 have complementary roles in maintaining proper 3′ overhang length.Rikard RunnbergSaishyam NarayananMarita CohnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rikard Runnberg Saishyam Narayanan Marita Cohn Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends
description	Abstract Telomere DNA ends with a single-stranded 3′ overhang. Long 3′ overhangs may cause aberrant DNA damage responses and accelerate telomere attrition, which is associated with cancer and aging, respectively. Genetic studies have indicated several important players in preventing 5′ end hyper-resection, yet detailed knowledge about the molecular mechanism in which they act is still lacking. Here, we use an in vitro DNA 5′ end protection assay, to study how N. castellii Cdc13 and Rap1 protect against 5′ exonucleolytic degradation by λ-exonuclease. The homogeneous telomeric repeat sequence of N. castellii allows us to study their protection ability at exact binding sites relative to the 5′ end. We find efficient protection by both Cdc13 and Rap1 when bound close to the 5′ end. Notably, Rap1 provides protection when binding dsDNA at a distance from the 5′ end. The DNA binding domain of Rap1 is sufficient for 5′ end protection, and its wrapping loop region is essential. Intriguingly, Rap1 facilitates protection also when its binding site contains 2 nt of ssDNA, thus spanning across the ds-ss junction. These results highlight a role of Rap1 in 5′ end protection and indicate that Cdc13 and Rap1 have complementary roles in maintaining proper 3′ overhang length.
format	article
author	Rikard Runnberg Saishyam Narayanan Marita Cohn
author_facet	Rikard Runnberg Saishyam Narayanan Marita Cohn
author_sort	Rikard Runnberg
title	Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends
title_short	Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends
title_full	Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends
title_fullStr	Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends
title_full_unstemmed	Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends
title_sort	rap1 and cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ea94b149eb7b4623a8c3eeb2d766981c
work_keys_str_mv	AT rikardrunnberg rap1andcdc13havecomplementaryrolesinpreventingexonucleolyticdegradationoftelomere5ends AT saishyamnarayanan rap1andcdc13havecomplementaryrolesinpreventingexonucleolyticdegradationoftelomere5ends AT maritacohn rap1andcdc13havecomplementaryrolesinpreventingexonucleolyticdegradationoftelomere5ends
_version_	1718388989903241216

Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends

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