RAD51-associated Protein 1 (RAD51AP1) Interacts with the Meiotic Recombinase DMC1 through a Conserved Motif

Dunlop, Myun Hwa; Dray, Eloïse; Zhao, Weixing; Tsai, Miaw Sheue; Wiese, Claudia; Schild, David; Sung, Patrick

doi:10.1074/jbc.m111.290015

Cited by 22 publications

(33 citation statements)

References 43 publications

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“…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: 96%

“…The isolated RAD51AP1 cDNA sequence matched 100% for isoform 2 (transcript variant 2). 21,46 The RAD51AP1 cDNA was cloned into the p3xFLAG-CMV-10 vector (Invitrogen; gift from Dr. Mary Zhang). The p3XFLAG-CMV-10 vector was also used to ligate USP1.…”

Section: Cell Lines Plasmids and Chemical Reagentsmentioning

confidence: 99%

“…RAD51AP1 also interacts with and stimulates activity of the meiosis-specific recombinase DMC1, to enhance the HR repair in meiotic cells. 20,21 Whether the RAD51AP1 activity or stability is regulated by other factors is unknown. We provide evidence that RAD51AP1 interacts with USP1 through UAF1, and that stability of RAD51AP1 is promoted by USP1 and UAF1.…”

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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“…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: 96%

Section: Cell Lines Plasmids and Chemical Reagentsmentioning

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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“…Plasmids-Plasmids for the Escherichia coli expression of the full-length human RAD51AP1 and the F1, F2, and F3 fragments with N-terminal maltose-binding protein and C-terminal (His) 6 tags have been previously described (10). The C60 (residues 275-335) portion of RAD51AP1 was similarly cloned and expressed.…”

Section: Methodsmentioning

confidence: 99%

Mechanistic Insights into RAD51-associated Protein 1 (RAD51AP1) Action in Homologous DNA Repair

Dunlop

Dray

Zhao

et al. 2012

Journal of Biological Chemistry

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“…RAD51-associated protein 1 is a protein interacting with RAD51 (34,35), which is a key factor in homologous pairing and strand transfer of DNA in HR repair in mammalian cells (36,37). HIRIP3 (HIRA-interacting protein 3) is a protein that is closely related to HIRA (38), a histone chaperone that preferentially places the variant histone H3.3 in nucleosomes (39).…”

Section: Hat1 Is Physically and Functionally Associated With Hr Repaimentioning

confidence: 99%

Histone Acetyltransferase 1 Promotes Homologous Recombination in DNA Repair by Facilitating Histone Turnover

Yang

Liang

et al. 2013

Journal of Biological Chemistry

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Background: HAT1 is involved in homologous recombination repair. Results: HAT1 facilitates the incorporation of H4K5/K12-acetylated H3.3 at double-strand break sites through its HIRA-dependent histone turnover activity, thereby promoting efficient homologous recombination process. Conclusion: HAT1 is a key regulator of homologous recombination repair. Significance: This work provides a mechanistic insight into the regulation of histone dynamics by HAT1.

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RAD51-associated Protein 1 (RAD51AP1) Interacts with the Meiotic Recombinase DMC1 through a Conserved Motif

Cited by 22 publications

References 43 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

Mechanistic Insights into RAD51-associated Protein 1 (RAD51AP1) Action in Homologous DNA Repair

Histone Acetyltransferase 1 Promotes Homologous Recombination in DNA Repair by Facilitating Histone Turnover

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