Promotion of Homologous Recombination and Genomic Stability by RAD51AP1 via RAD51 Recombinase Enhancement

Wiese, Claudia; Dray, Eloïse; Groesser, Torsten; Filippo, Joseph San; Shi, Idina; Collins, David W.; Tsai, Miaw Sheue; Williams, Gareth J.; Rydberg, Björn; Sung, Patrick; Schild, David

doi:10.1016/j.molcel.2007.08.027

Cited by 128 publications

(246 citation statements)

References 32 publications

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“…RAD51AP1 knockdown is known to sensitize cells to Cisplatin (or MMC). 4,5 Consistently, we show that cells depleted of RAD51AP1 (using the 3 0 UTR targeting siRNA) shows increased chromosomal aberrations in response to MMC in U2OS cells (Fig. S6).…”

Section: Phenotypes Of Cells Expressing the Uaf1 Interactiondeficientsupporting

confidence: 75%

“…4,5,[19][20][21] Unlike the RAD51 paralogs (e.g. RAD51C), depletion of RAD51AP1 does not affect the foci formation of RAD51.…”

Section: Discussionmentioning

confidence: 97%

“…For example, RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) promotes the loading of RAD51 to ssDNA, 3 whereas RAD51AP1 (RAD51-Associated Protein 1) was suggested to function subsequent to the ssDNA-RAD51 nucleofilament formation. 4,5 The ubiquitin-proteasome system (UPS) is intimately implicated in the regulation of the DNA repair and DNA damage response. Deubiquitinating enzymes (DUBs) have emerged as an important class of regulators of the UPS.…”

Section: Introductionmentioning

confidence: 99%

“…Knockdown of RAD51AP1 in human cells or knockout in DT40 cells leads to enhanced sensitivity to IR or DNA interstrand crosslinking agents. 4,5,18 RAD51AP1 is not essential for foci formation of RAD51, 4,5,18 but by directly associating with RAD51 and DNA, it stimulates the RAD51-mediated D-loop formation, 4,5,19 which is an intermediate structure during HR repair. Thus, RAD51AP1 is suggested to act downstream of the RAD51-ssDNA nucleoprotein filament formation.…”

Section: Introductionmentioning

confidence: 99%

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The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair

et al. 2016

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USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interactiondeficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1.

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Section: Phenotypes Of Cells Expressing the Uaf1 Interactiondeficientsupporting

confidence: 75%

“…4,5,[19][20][21] Unlike the RAD51 paralogs (e.g. RAD51C), depletion of RAD51AP1 does not affect the foci formation of RAD51.…”

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair

et al. 2016

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“…Immunostaining for anti-RAD51 (sc-8349, Santa Cruz), anti-phospo-RPA (S4S8, Bethyl), anti-gH2AX (JBW301, Millipore), and anti-53BP1 (4937s, Cell Signaling) was performed as described previously. 24 …”

Section: Immunofluorescencementioning

confidence: 99%

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Betts

Marjaneh

Al-Ejeh

et al. 2017

The American Journal of Human Genetics

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Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

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Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis

Kawata

Shimazaki

Okabe

2008

Environ and Mol Mutagen

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Carcinogenesis is an important chronic toxicity of metals and metalloids, although their mechanisms of action are still unclear. Comparison of gene expression patterns induced by carcinogenic metals, metalloids, and model carcinogens would give an insight into understanding of their carcinogenic mechanisms. In this study, we examined the gene expression alteration in human hepatoma cell line, HepG2, after exposing to two metals (cadmium and nickel), a metalloid (arsenic), and three model carcinogenic chemicals N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA), and tetrachloroethylene (TCE) using DNA microarrays with 8,795 human genes. Of the genes altered by As, Cd, and Ni exposures, 31-55% were overlapped with those altered by three model carcinogenic chemical exposures in our experiments. In particular, the metals and metalloid shared certain characteristics with TPA and TCE in remarkable upregulations of the genes associated with progression of cell cycle, which might play a central role in As, Cd, and Ni carcinogenesis. This characteristic of gene expression alteration was partially counteracted by intracellular accumulation of vitamin C in Asexposed cells, whereas the number of cell-cycle associated genes was increased in Cd-and Niexposed cells. In our experimental conditions, ROS might have an accelerative effect on the cell proliferation mechanisms of As, but have an inhibitory effect on those of other two heavy metals. Furthermore, based on the results of Q-PCR, the oncogene PTTG1, which was upregulated by all carcinogenic chemical exposures in the array experiments, might be a useful biomarker for evaluation of the carcinogenesis of inorganic carcinogens. Environ. Mol. Mutagen. 50:46-59, 2009.

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Promotion of Homologous Recombination and Genomic Stability by RAD51AP1 via RAD51 Recombinase Enhancement

Cited by 128 publications

References 32 publications

The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair

The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis

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