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The CDC13-STN1-TEN1 complex stimulates Pol α activity by promoting RNA priming and primase-to-polymerase switch.

TitleThe CDC13-STN1-TEN1 complex stimulates Pol α activity by promoting RNA priming and primase-to-polymerase switch.
Publication TypeJournal Article
Year of Publication2014
AuthorsLue NF, Chan J, Wright WE, Hurwitz J
JournalNat Commun
Volume5
Pagination5762
Date Published2014 Dec 12
ISSN2041-1723
KeywordsBinding Sites, Candida glabrata, Cell Cycle Proteins, Chromosomal Proteins, Non-Histone, DNA Polymerase I, DNA Primase, DNA, Fungal, DNA, Single-Stranded, Fungal Proteins, Gene Expression Regulation, Fungal, Genome, Fungal, Genomic Instability, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, RNA, Fungal, Telomere, Telomere-Binding Proteins
Abstract

Emerging evidence suggests that Cdc13-Stn1-Ten1 (CST), an RPA-like ssDNA-binding complex, may regulate primase-Pol α (PP) activity at telomeres constitutively, and at other genomic locations under conditions of replication stress. Here we examine the mechanisms of PP stimulation by CST using purified complexes derived from Candida glabrata. While CST does not enhance isolated DNA polymerase activity, it substantially augments both primase activity and primase-to-polymerase switching. CST also simultaneously shortens the RNA and lengthens the DNA in the chimeric products. Stn1, the most conserved subunit of CST, is alone capable of PP stimulation. Both the N-terminal OB fold and the C-terminal winged-helix domains of Stn1 can bind to the Pol12 subunit of the PP complex and stimulate PP activity. Our findings provide mechanistic insights on a well-conserved pathway of PP regulation that is critical for genome stability.

DOI10.1038/ncomms6762
Alternate JournalNat Commun
PubMed ID25503194
PubMed Central IDPMC4269169
Grant ListNIH T32 CA124334 / CA / NCI NIH HHS / United States
AG01228 / AG / NIA NIH HHS / United States
R01 GM107287 / GM / NIGMS NIH HHS / United States
R01 AG001228 / AG / NIA NIH HHS / United States
R01 GM110083 / GM / NIGMS NIH HHS / United States
R01 GM069507 / GM / NIGMS NIH HHS / United States
NIH GM107287 / GM / NIGMS NIH HHS / United States
T32 CA124334 / CA / NCI NIH HHS / United States

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