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Brh2 promotes a template-switching reaction enabling recombinational bypass of lesions during DNA synthesis.

TitleBrh2 promotes a template-switching reaction enabling recombinational bypass of lesions during DNA synthesis.
Publication TypeJournal Article
Year of Publication2009
AuthorsMazloum N, Holloman WK
JournalMol Cell
Volume36
Issue4
Pagination620-30
Date Published2009 Nov 25
ISSN1097-4164
KeywordsDNA Damage, DNA Replication, DNA, Fungal, Fungal Proteins, Nucleic Acid Conformation, Rad51 Recombinase, Recombination, Genetic, Templates, Genetic, Ustilago
Abstract

Accumulating evidence for Rad51-catalyzed DNA strand invasion during double-strand break repair features a 3' single-stranded tail as the preferred substrate for reaction, but paradoxically, the preferred substrate in model reactions in vitro is the 5' end. Here, we examined the Rad51-promoted 5' end invasion reaction in the presence of Brh2, the BRCA2 family protein in Ustilago maydis. Using plasmid DNA and a homologous duplex oligonucleotide with 5' protruding single-stranded tail as substrates, we found that Brh2 can stimulate Rad51 to promote the formation of a four-stranded complement-stabilized D loop. In this structure, the incoming recessed complementary strand of the oligonucleotide has switched partners and can now prime DNA synthesis using the recipient plasmid DNA as template, circumventing a lesion that blocks elongation when the 5' protruding tail serves as template for fill-in synthesis. We propose that template switching promoted by Brh2 provides a mechanism for recombination-mediated bypass of lesions blocking synthesis during DNA replication.

DOI10.1016/j.molcel.2009.09.033
Alternate JournalMol. Cell
PubMed ID19941822
PubMed Central IDPMC2784892
Grant ListGM42482 / GM / NIGMS NIH HHS / United States
GM79859 / GM / NIGMS NIH HHS / United States
R01 GM042482-19 / GM / NIGMS NIH HHS / United States
R01 GM079859-03 / GM / NIGMS NIH HHS / United States

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