RecQ Helicase and Topoisomerase III Comprise a Novel DNA Strand Passage Function

Harmon, Frank G.; DiGate, Russell J.; Kowalczykowski, Stephen C.

doi:10.1016/s1097-2765(00)80354-8

Cited by 192 publications

(182 citation statements)

References 47 publications

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“…These biochemical observations support a role for BLM in preventing chromosome crossing-over by disrupting joint molecules before they mature into Holliday junctions. Our results and model do not deny the participation of BLM in these additional late functions; rather, the pleiotropic role of BLM in recombination is comparable with that of E. coli RecQ, which can act both early to initiate recombination and late to disrupt joint molecules and decatenate junctions (23,24).…”

Section: Discussionmentioning

confidence: 51%

“…BLM is a member of this RecQ family (16) and has been implicated in branch migration (17), disruption of joint molecules (18)(19)(20), and processing of double Holliday junctions by interaction with Rmi1 and topoisomerase III␣ (19,21,22), all late functions. However, E. coli RecQ functions both early and late in recombination (1,11,23) by stimulating RecJ (N. Handa, K. Morimatsu, S. T. Lovett, and S.C.K., unpublished observations) and cooperating with topoisomerase III (24), respectively. Thus, we examined whether BLM might also have multiple functions and could stimulate hExo1 to mimic RecQ and RecJ behavior functionally.…”

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confidence: 99%

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Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair

Nimonkar

Özsoy

Genschel³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

269

236

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The error-free repair of double-stranded DNA breaks by homologous recombination requires processing of broken ends. These processed ends are substrates for assembly of DNA strand exchange proteins that mediate DNA strand invasion. Here, we establish that human BLM helicase, a member of the RecQ family, stimulates the nucleolytic activity of human exonuclease 1 (hExo1), a 5 33 double-stranded DNA exonuclease. The stimulation is specific because other RecQ homologs fail to stimulate hExo1. Stimulation of DNA resection by hExo1 is independent of BLM helicase activity and is, instead, mediated by an interaction between the 2 proteins. Finally, we show that DNA ends resected by hExo1 and BLM are used by human Rad51, but not its yeast or bacterial counterparts, to promote homologous DNA pairing. This in vitro system recapitulates initial steps of homologous recombination and provides biochemical evidence for a role of BLM and Exo1 in the initiation of recombinational DNA repair.Bloom syndrome ͉ Rad51 ͉ recombination ͉ RecQ ͉ DNA pairing H omologous recombination contributes toward the maintenance of genomic integrity by accurately repairing doublestranded DNA (dsDNA) breaks. The recombinational repair of dsDNA breaks (DSBs) proceeds by successive reactions that start with processing of the broken DNA ends to reveal single-stranded DNA (ssDNA) (1). Processing requires the action of a helicase and/or nuclease. The resultant 3Ј-terminated ssDNA is used by a DNA strand exchange protein as the substrate for assembly of the nucleoprotein filament that is the active species in the search for homologous DNA and subsequent DNA pairing. It is unclear which enzymes in eukaryotes resect the DNA break to initiate recombination; however, much is known about the process in bacteria. In Escherichia coli, recombinational DNA repair occurs by either the RecBCD or the RecF pathway (1). RecBCD is a helicase/nuclease that processes dsDNA to produce 3Ј-tailed ssDNA onto which RecA is loaded. In the RecF pathway, a separate helicase and nuclease are used for resection of DSBs and ssDNA-gaps: RecQ, a 3Ј35Ј helicase, and RecJ, a 5Ј33Ј exonuclease (1).

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Section: Discussionmentioning

confidence: 51%

mentioning

confidence: 99%

Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair

Nimonkar

Özsoy

Genschel³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

269

236

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“…17, April 2006sage activity that can mediate decatenation of intertwined DNA molecules (Harmon et al, 1999(Harmon et al, , 2003. A related activity that dissolves two Holliday junctions has been described for human BLM helicase and TOPO III (Wu and Hickson, 2003).…”

Section: Discussionmentioning

confidence: 99%

Rad22^Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease

Coulon

Noguchi

et al. 2006

MBoC

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Slx1 and Slx4 are subunits of a structure-specific DNA endonuclease that is found in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and other eukaryotic species. It is thought to initiate recombination events or process recombination structures that occur during the replication of the tandem repeats of the ribosomal DNA (rDNA) locus. Here, we present evidence that fission yeast Slx1-Slx4 initiates homologous recombination events in the rDNA repeats that are processed by a mechanism that requires Rad22 (Rad52 homologue) but not Rhp51 (Rad51 homologue). Slx1 is required to generate ϳ50% of the spontaneous Rad22 DNA repair foci that occur in cycling cells. Most of these foci colocalize with the nucleolus, which contains the rDNA repeats. The increased fork pausing at the replication fork barriers in the rDNA repeats in a strain that lacks Rqh1 DNA helicase is further increased by expression of a dominant negative form of Slx1. These data suggest that Slx1-Slx4 cleaves paused replication forks in the rDNA, leading to Rad22-dependent homologous recombination that is used to maintain rDNA copy number. INTRODUCTIONWhile replicating the genome, DNA polymerases will sometimes stall when they encounter DNA lesions, protein complexes bound to DNA, or nucleotide starvation. Stalled forks pose serious threats to genomic integrity because they are prone to collapse or rearrangement (McGlynn and Lloyd, 2002). In contrast, there are many examples of natural replication pause and termination sites in a variety of organisms (Rothstein et al., 2000). These sites are often called replication fork barriers (RFBs). It is somewhat paradoxical that in some cases these "programmed" RFBs are thought to play important roles in maintaining genome integrity.The best-characterized RFBs occur in the ribosomal DNA genes (rDNA), which are present in long tandem repeats at one or a few chromosomal loci in most eukaryotic species, including yeasts and humans (Brewer and Fangman, 1988;Linskens and Huberman, 1988;Little et al., 1993;Gerber et al., 1997;Sanchez et al., 1998). The budding yeast Saccharomyces cerevisiae carries ϳ150 copies of the rDNA genes. The RFB is located in the nontranscribed sequence (NTS) between the 3Ј end of the 35S rRNA gene and the autonomously replicating sequence (ARS). The RFB inhibits replication fork progression in the direction opposite to rDNA transcription. This mechanism helps to prevent collisions between replication forks and the transcription machinery (Takeuchi et al., 2003). The protein fork blocking 1 (Fob1) binds DNA in the RFB region and is essential for RFB activity (Kobayashi and Horiuchi, 1996).The size of the rDNA array in S. cerevisiae is not static. For example, it will contract upon inactivation of RNA polymerase I and expands after RNA polymerase I activity is restored (Kobayashi et al., 1998). Fob1 is required for the mechanisms that control the copy number of rDNA repeats (Kobayashi et al., 2001;Johzuka and Horiuchi, 2002). The current model for the regulation of the rDNA copy number involv...

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“…No archaeal recQ homologues have been identified, but a functional counterpart of the protein may exist. It has been proposed that the functional interplay between topoisomerase and helicase may entail the recognition of DNA structures such as a Holliday junction and subsequent DNA unwinding by the helicase to provide substrates for the topoisomerase (Harmon et al, 1999;Wang, 2002). The topoisomerase may act to rewind the DNA, making necessary topological transformations, to facilitate the resolution of the DNA structures (Bennett and Wang, 2001).…”

Section: Discussionmentioning

confidence: 99%

Oligonucleotide cleavage and rejoining by topoisomerase III from the hyperthermophilic archaeon Sulfolobus solfataricus: temperature dependence and strand annealing‐promoted DNA religation

Chen

Huang²

2006

Molecular Microbiology

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SummaryTopoisomerase III from the hyperthermophilic archaeon Sulfolobus solfataricus ( Sso topo III) is optimally active in DNA relaxation at 75 ∞ C. We report here that Sso topo III-catalysed DNA cleavage and religation differed significantly in temperature dependence: the enzyme was most active in cleaving ssDNA containing a cleavage site at 25-50 ∞ C, but was efficient in rejoining the cleaved DNA strand only at higher temperatures (e.g. ≥ 45 ∞ C). The failure of Sso topo III to rejoin the cleaved DNA strand efficiently appeared to be responsible for the inability of the enzyme to relax negatively supercoiled DNA at low temperature (e.g. 25 ∞ C). Intriguingly, Sso topo III facilitated DNA annealing although it showed higher affinity for ssDNA than for dsDNA. Religation of the DNA strand cleaved by Sso topo III was drastically enhanced when the DNA was allowed to anneal to a complementary noncleaved oligonucleotide, presumably as a result of destabilization of the interaction between the enzyme and the cleaved strand through the formation of duplex DNA. A region in the non-cleaved strand corresponding to a sequence containing six bases on the 5 ¢ side and two bases on the 3 ¢ side of the cleavage site in the cleaved strand was crucial to the annealingpromoted religation. However, the annealing-promoted religation was relatively insensitive to mismatches in this region and the region conserved for oligonucleotide cleavage, except for that at the 5 ¢ end of the broken strand. These results suggest that Sso topo III is well suited for a role in DNA rewinding, whether it leads to homoduplex or heteroduplex formation.

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RecQ Helicase and Topoisomerase III Comprise a Novel DNA Strand Passage Function

Cited by 192 publications

References 47 publications

Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair

Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair

Rad22^Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease

Oligonucleotide cleavage and rejoining by topoisomerase III from the hyperthermophilic archaeon Sulfolobus solfataricus: temperature dependence and strand annealing‐promoted DNA religation

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RecQ Helicase and Topoisomerase III Comprise a Novel DNA Strand Passage Function

Cited by 192 publications

References 47 publications

Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair

Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair

Rad22Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease

Oligonucleotide cleavage and rejoining by topoisomerase III from the hyperthermophilic archaeon Sulfolobus solfataricus: temperature dependence and strand annealing‐promoted DNA religation

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About

Rad22^Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease