Mouse Rad54 affects DNA conformation and DNA-damage-induced Rad51 foci formation

Tan, Thomas; Essers, Jeroen; Citterio, Elisabetta; Swagemakers, Sigrid; Wit, Jan de; Benson, Fiona E.; Hoeijmakers, Jan H.J.; Kanaar, Roland

doi:10.1016/s0960-9822(99)80142-0

Cited by 187 publications

(192 citation statements)

References 16 publications

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“…Similar observations have been made with cells carrying mutations in BRCA1, RAD54, XRCC2 or XRCC3 (Bishop et al, 1998;Tan et al, 1999;Bhattacharyya et al, 2000;Huber et al, 2001;O'Regan et al, 2001). These studies indicate that the process of RAD51 focus formation in response to ionizing radiation (IR) may involve complex mechanisms of assembly that require many factors.…”

Section: Introductionsupporting

confidence: 61%

BRCA2-dependent and independent formation of RAD51 nuclear foci

2003

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The formation of RAD51 foci in response to ionizing radiation (IR) represents an important step in the repair of DNA double-strand breaks. RAD51 foci also appear during S phase and are thought to be required for the restart of stalled or broken replication forks. The RAD51 recombinase interacts directly with the breast cancerassociated tumour suppressor BRCA2, an interaction that is required for normal recombination proficiency, radiation resistance and genome stability. In CAPAN-1 cells, which express a truncated form of BRCA2 that is cytoplasmic because of loss of the nuclear localization signal, the formation of IR-induced RAD51 foci is impaired. In this work, we show that S-phase RAD51 foci form normally in CAPAN-1 cells expressing truncated BRCA2. Moreover, we find that RAD51 specifically associates with chromatin at S phase in a reaction that is BRCA2-independent. The observed BRCA2-dependent and independent formation of RAD51 foci shows that intact BRCA2 is not required for RAD51 focus formation per se, leading us to suggest that S phase and IR-induced RAD51 foci assemble by distinct pathways with defined protein requirements.

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Section: Introductionsupporting

confidence: 61%

BRCA2-dependent and independent formation of RAD51 nuclear foci

2003

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“…The RAD54 protein has ATPase activity and is related to DNA helicases; however, so far no in vitro helicase activity has been detected (Swagemakers et al, 1998). On the other hand, RAD54 does change the topological status of nicked plasmid DNA in vitro by demonstrating negative super-coiling activity (Tan et al, 1999). Thus, it is possible that RAD54 helps RAD51 and RAD52 unwind the DNA at the DSB to facilitate access of other repair factors.…”

Section: Mechanism Of Homologous Recombinationmentioning

confidence: 99%

“…The earliest recorded event (1-3 min) during foci formation is the phosphorylation of histone H2AX at S139 by ATM or other wortmannin-sensitive PIKKs Burma et al, 2001), followed by colocalization of BRCA1, RAD54, and either RAD50 or RAD51 (Scully et al, 1997a;Nelms et al, 1998;Tan et al, 1999;Gatei et al, 2000b;. Whether both ATM and ATR initiate H2AX phosphorylation necessary for DSB repair is uncertain (Mirzoeva and Petrini, 2001;.…”

Section: Atm Targets Involved In Dsb Repairmentioning

confidence: 99%

Regulation and mechanisms of mammalian double-strand break repair

2003

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The double-strand break (DSB) is believed to be one of the most severe types of DNA damage, and if left unrepaired is lethal to the cell. Several different types of repair act on the DSB. The most important in mammalian cells are nonhomologous end-joining (NHEJ) and homologous recombination repair (HRR). NHEJ is the predominant type of DSB repair in mammalian cells, as opposed to lower eucaryotes, but HRR has recently been implicated in critical cell signaling and regulatory functions that are essential for cell viability. Whereas NHEJ repair appears constitutive, HRR is regulated by the cell cycle and inducible signal transduction pathways. More is known about the molecular details of NHEJ than HRR in mammalian cells. This review focuses on the mechanisms and regulation of DSB repair in mammalian cells, the signaling pathways that regulate these processes and the potential crosstalk between NHEJ and HRR, and between repair and other stress-induced pathways with emphasis on the regulatory circuitry associated with the ataxia telangiectasia mutated (ATM) protein.

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“…Brca1 colocalizes with Rad51 in S phase and following DNA-damaging treatments (Scully et al, 1997), but this interaction is thought to be indirect and mediated by Brca2 (Venkitaraman, 2002). In addition, the helicase Rad54 participates in Rad51 foci formation following IR exposure, MMC or methyl methane sulphonate treatment, but is not required for their formation following UV irradiation (Tan et al, 1999). Therefore, it appears that the complexes involving Rad51 vary in relation to the cell cycle phase and/or the nature of the DNA lesion and could be involved in stress signalling or linking repair with the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

DNA damage induce γ-tubulin–RAD51 nuclear complexes in mammalian cells

et al. 2005

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Rad51 protein plays an essential role in recombination repair of DNA double-strand breaks and DNA crosslinking adducts. It is part of complexes which can vary with the stage of the cell cycle and the nature of the DNA lesions. During a search for Rad51-associated proteins in CHO nuclear extracts of S-phase cells by mass spectrometry of proteins immunoprecipitated with Rad51 antibodies, we identified a centrosomal protein, c-tubulin. This association was confirmed by the reverse immunoprecipitation with c-tubulin antibodies. Both proteins copurified from HeLa cells nuclear extracts following a tandem affinity purification of double-tagged Rad51. Immunofluorescence analysis showed colocalization of both Rad51 and c-tubulin in discrete foci in mammalian cell nuclei. The number of colocalized foci and their overlapping area increased in the presence of DNA damage produced by genotoxic treatments either during S phase or in exponentially growing cells. These variations did not result from an overall stress because microtubule cytoskeleton poisons devoid of direct interactions with DNA, such as taxol or colcemid, did not lead to an increase of this association. The recruitment of Rad51 and c-tubulin in the same nuclear complex suggests a link between DNA recombination repair and the centrosome function during the cell cycle.

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Mouse Rad54 affects DNA conformation and DNA-damage-induced Rad51 foci formation

Cited by 187 publications

References 16 publications

BRCA2-dependent and independent formation of RAD51 nuclear foci

BRCA2-dependent and independent formation of RAD51 nuclear foci

Regulation and mechanisms of mammalian double-strand break repair

DNA damage induce γ-tubulin–RAD51 nuclear complexes in mammalian cells

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