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Holliday junction-binding peptides inhibit distinct junction-processing enzymes.

ABSTRACT: Holliday junctions (HJ) are the central intermediates in both homologous recombination and site-specific recombination performed by tyrosine recombinases such as the bacteriophage lambda Integrase (Int) protein. Previously, our lab identified peptide inhibitors of Int-mediated recombination that prevent the resolution of HJ intermediates. We now show that two of these inhibitors bind HJ DNA in the square-planar conformation even in the absence of Int protein. The peptides prevent unwinding of branched DNA substrates by the RecG helicase of Escherichia coli and interfere with the resolution of HJ substrates by the RuvABC complex. Our results suggest that these peptides target all proteins that process HJ in the square-planar conformation. These inhibitors should be extremely useful for dissecting homologous recombination and recombination-dependent repair in vitro and in vivo.

SUBMITTER: Kepple KV

PROVIDER: S-EPMC1100769 | biostudies-literature | 2005 May

REPOSITORIES: biostudies-literature

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Holliday junction-binding peptides inhibit distinct junction-processing enzymes.

Kepple Kevin V KV Boldt Jeffrey L JL Segall Anca M AM

Proceedings of the National Academy of Sciences of the United States of America 20050502 19

Holliday junctions (HJ) are the central intermediates in both homologous recombination and site-specific recombination performed by tyrosine recombinases such as the bacteriophage lambda Integrase (Int) protein. Previously, our lab identified peptide inhibitors of Int-mediated recombination that prevent the resolution of HJ intermediates. We now show that two of these inhibitors bind HJ DNA in the square-planar conformation even in the absence of Int protein. The peptides prevent unwinding of br ...[more]

PMID: 15867153

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