The role of poly ADP-ribosylation in the first wave of DNA damage response

Liu, Chao; Vyas, Aditi; Kassab, Muzaffer Ahmad; Singh, Anup K.; Yu, Xiaochun

doi:10.1093/nar/gkx565

Cited by 189 publications

(207 citation statements)

References 185 publications

(187 reference statements)

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“…S3 A and B). The later RAP80-independent BRCA1 PARsylation interval is particularly interesting, since the majority of DNA damage-associated poly-ADP-ribosylation is known to occur within seconds to minutes after DNA damage and to be short-lived due to rapid de-PARsylation (28). Thus, in one model these results are consistent with the possibility that BRCA1 PARsylation and de-PARsylation contribute to the respective assembly and dissociation of BRCA1-containing complexes in IRIF in a finely organized temporal order following the onset of DNA damage (see the model in Fig.…”

Section: Resultsmentioning

confidence: 99%

RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci

Vohhodina

Toomire

Petit

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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BRCA1 promotes error-free, homologous recombination-mediated repair (HRR) of DNA double-stranded breaks (DSBs). When excessive and uncontrolled, BRCA1 HRR activity promotes illegitimate recombination and genome disorder. We and others have observed that the BRCA1-associated protein RAP80 recruits BRCA1 to postdamage nuclear foci, and these chromatin structures then restrict the amplitude of BRCA1-driven HRR. What remains unclear is how this process is regulated. Here we report that both BRCA1 poly-ADP ribosylation (PARsylation) and the presence of BRCA1-bound RAP80 are critical for the normal interaction of BRCA1 with some of its partners (e.g., CtIP and BACH1) that are also known components of the aforementioned focal structures. Surprisingly, the simultaneous loss of RAP80 and failure therein of BRCA1 PARsylation results in the dysregulated accumulation in these foci of BRCA1 complexes. This in turn is associated with the intracellular development of a state of hyper-recombination and gross chromosomal disorder. Thus, physiological RAP80-BRCA1 complex formation and BRCA1 PARsylation contribute to the kinetics by which BRCA1 HRR-sustaining complexes normally concentrate in nuclear foci. These events likely contribute to aneuploidy suppression.

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Section: Resultsmentioning

confidence: 99%

RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci

Vohhodina

Toomire

Petit

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Second, PAR may also act as a scaffold for recruiting other proteins. Indeed, a number of PAR-binding motifs (PBMs) have been identified, including WWE, PBZ, BRCT, macrodomain and OB-fold (Gibson and Kraus, 2012, Liu et al, 2017). These PBMs are present in many proteins involved in DDR.…”

Section: Introductionmentioning

confidence: 99%

A Cell-Line-Specific Atlas of PARP-Mediated Protein Asp/Glu-ADP-Ribosylation in Breast Cancer

Zhen

Zhang

2017

Cell Reports

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Summary PARP1 plays a critical role in regulating many biological processes linked to cellular stress responses. Although DNA strand breaks are potent stimuli of PARP1 enzymatic activity, the context-dependent mechanism regulating PARP1 activation and signaling is poorly understood. We performed global characterization of the PARP1-dependent, Asp/Glu-ADP-ribosylated proteome in a panel of cell lines originating from benign breast epithelial cells, as well as common subtypes of breast cancer. From these analyses, we identified 503 specific ADP-ribosylation sites on 322 proteins. Despite similar expression levels, PARP1 is differentially activated in these cell lines under genotoxic conditions, which generates signaling outputs with substantial heterogeneity. By comparing protein abundances and ADP-ribosylation levels, we could dissect cell-specific PARP1 targets that are driven by unique expression patterns vs. cell-specific regulatory mechanisms of PARylation. Intriguingly, PARP1 modifies many proteins in a cell-specific manner, including those involved in transcriptional regulation, mRNA metabolism, and protein translation.

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“…Our study revealed methylated UHRF1 is recruited to DNA damage sites in a PARP1-dependent manner to contribute to the DNA repair pathway. This indicates the early stage of DDR is initiated by PARylation and the interaction between PARP1 and UHRF1 proceeds with the later stage of this DSB repair process for HR function (17).…”

Section: Discussionmentioning

confidence: 95%

“…We suggested unmethylated UHRF1 failed to function in the HR system owing to defective binding to PARP1 as well as inhibited PCNA polyubiquitination. Moreover, following the studies of the antagonistic methylation regulation by SET7 and LSD1 (6,17,18), we investigated whether LSD1-mediated UHRF1 demethylation could play a role in preventing the interaction between PARP1 and UHRF1. Notably, we showed LSD1 knockdown or specific inhibition using GSK-LSD1 facilitated the association of PARP1 and UHRF1.…”

Section: Discussionmentioning

confidence: 99%

Methylated-UHRF1 and PARP1 Interaction Is Critical for Homologous Recombination

et al. 2020

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A recent study suggested that methylation of ubiquitin-like with PHD and RING finger domain 1 (UHRF1) is regulated by SET7 and lysine-specific histone demethylase 1A (LSD1) and is essential for homologous recombination (HR). The study demonstrated that SET7-mediated methylation of UHRF1 promotes polyubiquitination of proliferating cell nuclear antigen (PCNA), inducing HR. However, studies on mediators that interact with and recruit UHRF1 to damaged lesions are needed to elucidate the mechanism of UHRF1 methylationinduced HR. Here, we identified that poly [ADP-ribose] polymerase 1 (PARP1) interacts with damage-induced methylated UHRF1 specifically and mediates UHRF1 to induce HR progression. Furthermore, cooperation of UHRF1-PARP1 is essential for cell viability, suggesting the importance of the interaction of UHRF1-PARP1 for damage tolerance in response to damage. Our data revealed that PARP1 mediates the HR mechanism, which is regulated by UHRF1 methylation. The data also indicated the significant role of PARP1 as a mediator of UHRF1 methylation-correlated HR pathway. [BMB Reports 2020; 53(2): 112-117] BMB Rep. 2020; 53(2): 112-117 www.bmbreports.org UHRF1 and PARP1 promote homologous recombination Ja Young Hahm, et al. 113 http://bmbreports.org BMB Reports

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The role of poly ADP-ribosylation in the first wave of DNA damage response

Cited by 189 publications

References 185 publications

RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci

RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci

A Cell-Line-Specific Atlas of PARP-Mediated Protein Asp/Glu-ADP-Ribosylation in Breast Cancer

Methylated-UHRF1 and PARP1 Interaction Is Critical for Homologous Recombination

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