Multimerization domains are associated with apparent strand exchange activity in BLM and WRN DNA helicases

Chi Fu Chen, Steven J. Brill

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

BLM and WRN are members of the RecQ family of DNA helicases that act to suppress genome instability and cancer predisposition. In addition to a RecQ helicase domain, each of these proteins contains an N-terminal domain of approximately 500 amino acids (aa) that is incompletely characterized. Previously, we showed that the N-terminus of Sgs1, the yeast ortholog of BLM, contains a physiologically important 200 aa domain (Sgs1103-322) that displays single-stranded DNA (ssDNA) binding, strand annealing (SA), and apparent strand-exchange (SE) activities in vitro. Here we used a genetic assay to search for heterologous proteins that could functionally replace this domain of Sgs1 in vivo. In contrast to Rad59, the oligomeric Rad52 protein provided in vivo complementation, suggesting that multimerization is functionally important. An N-terminal domain of WRN was also identified that could replace Sgs1103-322 in yeast. This domain, WRN235-526, contains a known coiled coil and displays the same SA and SE activities as Sgs1103-322. The coiled coil domain of WRN235-526 is required for both its in vivo activity and its in vitro SE activity. Based on this result, a potential coiled coil was identified within Sgs1103-322. This 25 amino acid region was similarly essential for wt Sgs1 activity in vivo and was replaceable by a heterologous coiled coil. Taken together, the results indicate that a coiled coil and a closely linked apparent SE activity are conserved features of the BLM and WRN DNA helicases.

Original languageEnglish (US)
Pages (from-to)137-146
Number of pages10
JournalDNA Repair
Volume22
DOIs
StatePublished - Oct 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Keywords

  • DNA helicase
  • DNA recombination
  • DNA strand exchange
  • Genomic instability
  • Protein nucleic acid interaction
  • Yeast genetics

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