p53 is directly linked to homologous recombination processes via RAD51/RecA protein interaction

Stürzbecher, Horst‐Werner; Donzelmann, Beate; Buchhop, Sabine

doi:10.1007/bf02572002

Cited by 77 publications

(90 citation statements)

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“…That means that specific interaction among these proteins is a reliable fact; thus, specific interaction between Rad51 and Rad52 has been demonstrated, suggesting that Rad52 may modulate the catalytic activities of Rad51 protein, this interaction being species-specific (Shinohara et al, 1993;Shen et al, 1996). Evidence of specific protein-protein association between p53 and human Rad51 protein has been reported (Stürzbecher et al, 1996). More recentl it has been established that BRCA2 and p53 proteins exist in vivo in the same complexes, and that functional interaction between BRCA2 and p53 is a fact, demonstrated by evidence that BRCA2 inhibits p53 transcriptional activity in cancer cells; in this wa Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations coexpression of Rad51 enhances BRCA2's inhibitory effects (Marmorstein et al, 1998).…”

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confidence: 98%

Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations

et al. 1999

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Summary Loss of heterozygosity (LOH) in loci of the 15q15.1, 12p13, 1p32, 17q21 and 13q12-13 regions may collaborate in the inactivatio n of RAD51, RAD52, RAD54, BRCA1, BRCA2 and possibly other genes implicated in the repair of double-stranded DNA and in DNA recombination. We investigate allelic losses in microsatellites of the RAD51, RAD52, RAD54, BRCA1 and BRCA2 regions, and their correlations with nine pathologic parameters in 127 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using 15 markers of the 15q15.1, 12p13.3, 1p32, 17q21 and 13q12-13 regions. LOH was found in the RAD51 region in 32% of tumours, in t he RAD52 region in 16%, in RAD54 in 20% and in the BRCA1 and BRCA2 regions in 49% and 44% respectivel y. Significant correlations between one or more regions with concomitant LOH and pathologic parameters were observed with respect to age (P = 0.008), oestrogen receptor content (P = 0.03), progesterone receptors (P = 0.003), higher grade (P = 0.001), more advanced stage (P = 0.004) and peritumoural vessel involvement (P < 0.0001). The number of cases in which LOH was observed simultaneously in two or more regions was always higher than expected on the basis of their statistical probabilit y, and curiousl y, the three patients with LOH at five regions concomi tantly were under the age of 30 years. These results suggest that LOH at these regions could be related to breast cance r, and probably to a poo r tumour prognosis .

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confidence: 98%

Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations

et al. 1999

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“…However, while growA differences might be ascribed to influences other than p53 activity, it seems less likely that the enhanced recombination suppression observed for the p53 +/m MEFs relative to p53+/− MEFs is due to non-p53 influences, since this is a relatively specific activity. We and others have shown that an important function of wild-type p53 is to suppress homologous recombination (Sturzbecher et al, 1996;Mekeel et al, 1997;Bertrand et al, 1997;Saintigny et al, 1999;Lu et al, 2003). The C-terminus of p53 binds directly to recombination intermediates in vitro and both homologous and non-homologous end joining processes are inhibited by p53 Yang et al, 2002).…”

Section: Discussionmentioning

confidence: 97%

“…Such events can be scored by cells showing GFP fluorescence or zeocin plus G418 drug resistance. This vector, when transduced as a single copy into target cells, is an indicator of genomic instability and is particularly relevant in this context since wild-type p53 has been shown to suppress homologous recombination events (Sturzbecher et al, 1996;Mekeel et al, 1997;Bertrand et al, 1997;Saintigny et al, 1999;Lu et al, 2003). After infection with the Neo-GFP-Zeo retroviral vector, MEFs were selected in G418 or G418 plus zeocin and the number of zeocin resistant colonies per 10 6 G418 colonies was calculated.…”

Section: P53+/m Mefs Exhibit Slower Growth Kinetics Enhanced Cell Cymentioning

confidence: 99%

Aging-associated truncated form of p53 interacts with wild-type p53 and alters p53 stability, localization, and activity

Moore

Ghebranious

et al. 2007

Mechanisms of Ageing and Development

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Evidence has accumulated that p53, a prototypical tumor suppressor, may also influence aspects of organismal aging. We have previously described a p53 mutant mouse model, the p53+/m mouse, which is cancer resistant yet exhibits reduced longevity and premature aging phenotypes. p53+/m mice express one full length p53 allele and one truncated p53 allele that is translated into a C-terminal fragment of p53 termed the M protein. The augmented cancer resistance and premature aging phenotypes in the p53+/m mice are consistent with a hyperactive p53 state. To determine how the M protein could increase p53 activity, we examined the M protein in various cellular contexts. Here, we show that embryo fibroblasts from p53+/m mice exhibit reduced proliferation and cell cycle progression compared to embryo fibroblasts from p53+/− mice (with equivalent wild-type p53 dosage). The M protein interacts with wild-type p53, increases its stability, and facilitates its nuclear localization in the absence of stress. Despite increasing p53 stability, the M protein does not disrupt p53-Mdm2 interactions and does not prevent p53 ubiquitination. These results suggest molecular mechanisms by which the M protein could influence the aging and cancer resistance phenotypes in the p53+/m mouse.

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“…RAD51 is expressed in proliferating cells with the highest level in the S or S/G 2 phase of the cell cycle [11][12][13]. Specific interaction between RAD51 and such proteins as BRCA1, BRCA2, p53 and RAD52 has been described [14][15][16][17][18]. BRCA1 was shown to bind with RAD51 and co-localize with RAD51 in mitotic and meiotic cells [19,20].…”

Section: Introductionmentioning

confidence: 99%

Genetic instability in the RAD51 and BRCA1 regions in breast cancer

Nowacka-Zawisza

Bryś

Romanowicz-Makowska

et al. 2007

Cellular and Molecular Biology Letters

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Abbreviations used: AML -acute myeloid leukemia; BACH1 helicase -BRCA1 interacting protein C-terminal helicase 1 [Homo sapiens]; BRCA1 -breast cancer susceptibility gene 1; BRCT -BRCA C-terminus; LOH -loss of heterozygosity; RecA -RecA protein (Recombinase A); MRE11 -meiotic recombination 11 homologue A; NBS1 -Nijmegen breakage syndrome 1 (nibrin, NBN); p53 -tumor protein 53; RAD50 -RAD50 homologue (Saccharomyces cerevisiae) [ Abstract: Breast cancer is the most prevalent cancer type in women. Accumulating evidence indicates that the fidelity of double-strand break repair in response to DNA damage is an important step in mammary neoplasias. The RAD51 and BRCA1 proteins are involved in the repair of double-strand DNA breaks by homologous recombination. In this study, we evaluated loss of heterozygosity (LOH) in the RAD51 and BRCA1 regions, and their association with breast cancer. The polymorphic markers D15S118, D15S214 and D15S1006 were the focus for RAD51, and D17S855 and D17S1323 for BRCA1. Genomic deletion detected by allelic loss varied according to the regions tested, and ranged from 29 to 46% of informative cases for the RAD51 region and from 38 to 42% of informative cases for the BRCA1 region. 25% of breast cancer cases displayed LOH for at least one studied marker in the RAD51 region exclusively. On the other hand, 31% of breast cancer cases manifested LOH for at least one microsatellite marker concomitantly in the RAD51 and BRCA1 regions. LOH in the RAD51 region,

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p53 is directly linked to homologous recombination processes via RAD51/RecA protein interaction

Cited by 77 publications

References 0 publications

Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations

Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations

Aging-associated truncated form of p53 interacts with wild-type p53 and alters p53 stability, localization, and activity

Genetic instability in the RAD51 and BRCA1 regions in breast cancer

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