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Polarity and Bypass of DNA Heterology during Branch Migration of Holliday Junctions by Human RAD54, BLM, and RECQ1 Proteins
Journal article   Open access   Peer reviewed

Polarity and Bypass of DNA Heterology during Branch Migration of Holliday Junctions by Human RAD54, BLM, and RECQ1 Proteins

Olga M Mazina, Matthew J Rossi, Julianna S Deakyne, Fei Huang and Alexander V Mazin
The Journal of biological chemistry, v 287(15), pp 11820-11832
06 Apr 2012
PMID: 22356911
url
https://doi.org/10.1074/jbc.M112.341347View
Published, Version of Record (VoR) Open

Abstract

DNA and Chromosomes DNA Repair DNA-Protein Interaction Homologous Recombination DNA-binding Protein ATPases DNA Recombination DNA Helicase
Background: Several proteins catalyze branch migration (BM) of the Holliday junction. Results: RAD54 is a robust BM protein capable of bypassing extensive regions of DNA heterology. RAD54, BLM, and RECQ1 drive BM in the 3′→5′ direction. Conclusion: The displacement strand of joint molecules (JMs) defines the polarity of BM. Significance: BM is mechanistically distinct from helicase activity of DNA translocating proteins. Several proteins have been shown to catalyze branch migration (BM) of the Holliday junction, a key intermediate in DNA repair and recombination. Here, using joint molecules made by human RAD51 or Escherichia coli RecA, we find that the polarity of the displaced ssDNA strand of the joint molecules defines the polarity of BM of RAD54, BLM, RECQ1, and RuvAB. Our results demonstrate that RAD54, BLM, and RECQ1 promote BM preferentially in the 3′→5′ direction, whereas RuvAB drives it in the 5′→3′ direction relative to the displaced ssDNA strand. Our data indicate that the helicase activity of BM proteins does not play a role in the heterology bypass. Thus, RAD54 that lacks helicase activity is more efficient in DNA heterology bypass than BLM or REQ1 helicases. Furthermore, we demonstrate that the BLM helicase and BM activities require different protein stoichiometries, indicating that different complexes, monomers and multimers, respectively, are responsible for these two activities. These results define BM as a mechanistically distinct activity of DNA translocating proteins, which may serve an important function in DNA repair and recombination.

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Domestic collaboration
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Web of Science research areas
Biochemistry & Molecular Biology
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