Physical and functional interactions of caenorhabditis elegans WRN-1 helicase with RPA-1

Moonjung Hyun, Sojin Park, Eunsun Kim, Do Hyung Kim, Se Jin Lee, Hyeon Sook Koo, Yeon Soo Seo, Byungchan Ahn

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Abstract

The Caenorhabditis elegans Werner syndrome protein, WRN-1, a member of the RecQ helicase family, has a 3′-5′ DNA helicase activity. Worms with defective wrn-1 exhibit premature aging phenotypes and an increased level of genome instability. In response to DNA damage, WRN-1 participates in the initial stages of checkpoint activation in concert with C. elegans replication protein A (RPA-1). WRN-1 helicase is stimulated by RPA-1 on long DNA duplex substrates. However, the mechanism by which RPA-1 stimulates DNA unwinding and the function of the WRN-1-RPA-1 interaction are not clearly understood. We have found that WRN-1 physically interacts with two RPA-1 subunits, CeRPA73 and CeRPA32; however, full-length WRN-1 helicase activity is stimulated by only the CeRPA73 subunit, while the WRN-1 162-1056 fragment that harbors the helicase activity requires both the CeRPA73 and CeRPA32 subunits for the stimulation. We also found that the CeRPA73 1-464 fragment can stimulate WRN-1 helicase activity and that residues 335-464 of CeRPA73 are important for physical interaction with WRN-1. Because CeRPA73 and the CeRPA73 1-464 fragment are able to bind single-stranded DNA (ssDNA), the stimulation of WRN-1 helicase by RPA-1 is most likely due to the ssDNA binding activity of CeRPA73 and the direct interaction of WRN-1 and CeRPA73.

Original languageEnglish
Pages (from-to)1336-1345
Number of pages10
JournalBiochemistry
Volume51
Issue number7
DOIs
Publication statusPublished - 2012 Feb 21

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All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Hyun, M., Park, S., Kim, E., Kim, D. H., Lee, S. J., Koo, H. S., Seo, Y. S., & Ahn, B. (2012). Physical and functional interactions of caenorhabditis elegans WRN-1 helicase with RPA-1. Biochemistry, 51(7), 1336-1345. https://doi.org/10.1021/bi200791p