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Combinatorial recognition of a complex telomere repeat sequence by the Candida parapsilosis Cdc13AB heterodimer.

TitleCombinatorial recognition of a complex telomere repeat sequence by the Candida parapsilosis Cdc13AB heterodimer.
Publication TypeJournal Article
Year of Publication2015
AuthorsSteinberg-Neifach O, Wellington K, Vazquez L, Lue NF
JournalNucleic Acids Res
Volume43
Issue4
Pagination2164-76
Date Published2015 Feb 27
ISSN1362-4962
KeywordsCandida, DNA, Fungal, Fungal Proteins, Protein Multimerization, Protein Structure, Tertiary, Repetitive Sequences, Nucleic Acid, Telomere, Telomere-Binding Proteins
Abstract

The telomere repeat units of Candida species are substantially longer and more complex than those in other organisms, raising interesting questions concerning the recognition mechanisms of telomere-binding proteins. Herein we characterized the properties of Candida parapsilosis Cdc13A and Cdc13B, two paralogs that are responsible for binding and protecting the telomere G-strand tails. We found that Cdc13A and Cdc13B can each form complexes with itself and a heterodimeric complex with each other. However, only the heterodimer exhibits high-affinity and sequence-specific binding to the telomere G-tail. EMSA and crosslinking analysis revealed a combinatorial mechanism of DNA recognition, which entails the A and B subunit making contacts to the 3' and 5' region of the repeat unit. While both the DBD and OB4 domain of Cdc13A can bind to the equivalent domain in Cdc13B, only the OB4 complex behaves as a stable heterodimer. The unstable Cdc13AB(DBD) complex binds G-strand with greatly reduced affinity but the same sequence specificity. Thus the OB4 domains evidently contribute to binding by promoting dimerization of the DBDs. Our investigation reveals a rare example of combinatorial recognition of single-stranded DNA and offers insights into the co-evolution of telomere DNA and cognate binding proteins.

DOI10.1093/nar/gkv092
Alternate JournalNucleic Acids Res
PubMed ID25662607
PubMed Central IDPMC4344524

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