Disruptive influence

Foiani, Marco

doi:10.1038/423234a

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…The manner in which BRCA1 affects HR efficiency is not yet understood. Genetic analyses have revealed that HR is subject to enhancement and negative regulation by a number of DNA helicases (5,58), and ongoing studies are beginning to elucidate the HR function of these helicases (21, 58 -61). It remains to be seen whether Rad54 acts alone or in conjunction with other factors (e.g.…”

Section: Epiloguementioning

confidence: 99%

Rad51 Recombinase and Recombination Mediators

Sung

Krejčí

Komen

et al. 2003

Journal of Biological Chemistry

382

349

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Section: Epiloguementioning

confidence: 99%

Rad51 Recombinase and Recombination Mediators

Sung

Krejčí

Komen

et al. 2003

Journal of Biological Chemistry

382

349

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“…Whereas some proteins promote HR (14, 31), others inhibit this process, thereby preventing its untimely initiation (32,33). Disruption of the Rad51-ssDNA nucleoprotein filament appears to be an especially important mechanism of controlling HR.…”

mentioning

confidence: 99%

Bloom Syndrome Helicase Stimulates RAD51 DNA Strand Exchange Activity through a Novel Mechanism

Bugreev

Mazina

Mazin

2009

Journal of Biological Chemistry

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Loss or inactivation of BLM, a helicase of the RecQ family, causes Bloom syndrome, a genetic disorder with a strong predisposition to cancer. Although the precise function of BLM remains unknown, genetic data has implicated BLM in the process of genetic recombination and DNA repair. Previously, we demonstrated that BLM can disrupt the RAD51-singlestranded DNA filament that promotes the initial steps of homologous recombination. However, this disruption occurs only if RAD51 is present in an inactive ADP-bound form. Here, we investigate interactions of BLM with the active ATP-bound form of the RAD51-single-stranded DNA filament. Surprisingly, we found that BLM stimulates DNA strand exchange activity of RAD51. In contrast to the helicase activity of BLM, this stimulation does not require ATP hydrolysis. These data suggest a novel BLM function that is stimulation of the RAD51 DNA pairing. Our results demonstrate the important role of the RAD51 nucleoprotein filament conformation in stimulation of DNA pairing by BLM.Mutations of BLM helicase cause Bloom syndrome (BS), 2 a rare autosomal disorder, which is associated with stunted growth, facial sun sensitivity, immunodeficiency, fertility defects, and a greatly elevated incidence of many types of cancer occurring at an early age (1). BLM belongs to the highly conserved family of RecQ helicases that are required for the maintenance of genome integrity in all organisms (2, 3). There are five RecQ helicases in humans; mutations in three of them, WRN, RECQ4, and BLM, have been associated with the genetic abnormalities known as Werner, Rothmund-Thomson, and Bloom syndrome, respectively (4, 5). The cells from BS patients display genomic instability; the hallmark of BS is an increase in the frequency of sister chromatid and interhomolog exchanges (1, 6). Because homologous recombination (HR) is responsible for chromosomal exchanges, it is thought that BLM helicase functions in regulating HR (7-9). Also, BLM helicase is required for faithful chromosome segregation (10) and repair of stalled replication forks (11, 12), the processes that are linked to HR (13-15). BLM was found to interact physically with RAD51, a key protein of HR (16) that catalyzes the central steps in HR including the search for homology and the exchange of strands between homologous ssDNA and dsDNA sequences (17). In cells, BLM forms nuclear foci, a subset of which co-localize with RAD51. Interestingly, the extent of RAD51 and BLM co-localization increases in response to ionizing radiation, indicating a possible role of BLM in the repair of DNA double-strand breaks (16).Biochemical studies suggest that BLM may perform several different functions in HR. BLM was shown to promote the dissociation of HR intermediates (D-loops) (18 -20), branch migration of Holliday junctions (21), and dissolution of double Holliday junctions acting in a complex with . BLM may also facilitate DNA synthesis during the repair process by unwinding the DNA template in front of the replication fork (25). In addition, BLM and its yea...

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Cell death promoted by homologous DNA interaction from bacteria to humans

Kusano¹

2004

Advances in Biophysics

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Disruptive influence

Cited by 3 publications

References 13 publications

Rad51 Recombinase and Recombination Mediators

Rad51 Recombinase and Recombination Mediators

Bloom Syndrome Helicase Stimulates RAD51 DNA Strand Exchange Activity through a Novel Mechanism

Cell death promoted by homologous DNA interaction from bacteria to humans

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