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

Neal F. Lue, Jamie Chan, Woodring E. Wright, Jerard Hurwitz

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Article number5762
JournalNature Communications
Volume5
DOIs
StatePublished - 2014

Fingerprint

DNA Primase
priming
switches
Switches
RNA
stimulation
deoxyribonucleic acid
telomeres
genome
helices
emerging
Candida glabrata
Candida
Genomic Instability
Telomere
DNA-Directed DNA Polymerase
products
Genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

The CDC13-STN1-TEN1 complex stimulates Pol α activity by promoting RNA priming and primase-to-polymerase switch. / Lue, Neal F.; Chan, Jamie; Wright, Woodring E.; Hurwitz, Jerard.

In: Nature Communications, Vol. 5, 5762, 2014.

Research output: Contribution to journalArticle

Lue, Neal F. ; Chan, Jamie ; Wright, Woodring E. ; Hurwitz, Jerard. / The CDC13-STN1-TEN1 complex stimulates Pol α activity by promoting RNA priming and primase-to-polymerase switch. In: Nature Communications. 2014 ; Vol. 5.
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