Function of BRCA1 in the DNA Damage Response Is Mediated by ADP-Ribosylation

Li, Mo; Yu, Xiaochun

doi:10.1016/j.ccr.2013.03.025

Cited by 278 publications

(289 citation statements)

References 71 publications

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“…S9A). This is consistent with other findings that PAR also mediates the fast recruitment of other DNA damage repair factors to DNA lesions (15,16). To examine the nature of the relatively fast DNA damage repair mediated by hSSB1, we used siRNA to deplete XRCC1, a key factor for ssDNA damage repair (33-37).…”

Section: Ints3supporting

confidence: 59%

“…Recent evidence suggests that DNA damage-induced PAR may serve as a docking signal to recruit DDR factors to DNA lesions (7)(8)(9)(10)(11)(12)(13)(14). For example, our recent study showed that the BRCT domains of BARD1 and NBS1 recognize PAR, which facilitates the rapid recruitment of the BRCA1/BARD1 complex and NBS1 to the site of DNA damage (15,16). These results indicate that other DDR factors may also be recruited to DNA damage sites by PAR.…”

mentioning

confidence: 84%

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The oligonucleotide/oligosaccharide-binding fold motif is a poly(ADP-ribose)-binding domain that mediates DNA damage response

Zhang

Chen

et al. 2014

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

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Oligonucleotide/oligosaccharide-binding (OB) fold is a ssDNA or RNA binding motif in prokaryotes and eukaryotes. Unexpectedly, we found that the OB fold of human ssDNA-binding protein 1 (hSSB1) is a poly(ADP ribose) (PAR) binding domain. hSSB1 exhibits highaffinity binding to PAR and recognizes iso-ADP ribose (ADPR), the linkage between two ADPR units. This interaction between PAR and hSSB1 mediates the early recruitment of hSSB1 to the sites of DNA damage. Mutations in the OB fold of hSSB1 that disrupt PAR binding abolish the relocation of hSSB1 to the sites of DNA damage. Moreover, PAR-mediated recruitment of hSSB1 is important for early DNA damage repair. We have screened other OB folds and found that several other OB folds also recognize PAR. Taken together, our study reveals a PAR-binding domain that mediates DNA damage repair.G enomic integrity is constantly challenged by various types of DNA damage, which are induced by DNA replication errors, environmental hazards, and other genotoxic stress. In response to this stress, cells activate an evolutionarily conserved pathway termed the DNA damage response (DDR), to orchestrate various cellular responses for maintaining genomic stability (1-3). It has been shown that poly(ADP ribosyl)ation plays an important role in DDR (4-6). Upon DNA damage induction, poly(ADP ribose) (PAR) polymerases (PARPs), such as PARP1, the founding member of the PARP family, rapidly detect DNA breaks, including single-strand breaks (SSBs) and double-strand breaks (DSBs), and activate PAR synthesis at or adjacent to DNA lesions (7,8). Recent evidence suggests that DNA damage-induced PAR may serve as a docking signal to recruit DDR factors to DNA lesions (7-14). For example, our recent study showed that the BRCT domains of BARD1 and NBS1 recognize PAR, which facilitates the rapid recruitment of the BRCA1/BARD1 complex and NBS1 to the site of DNA damage (15, 16). These results indicate that other DDR factors may also be recruited to DNA damage sites by PAR. Thus, it is important to identify other "readers" of PAR to elucidate the molecular mechanism of PAR in DDR.Previous studies have shown that human ssDNA-binding protein 1 (hSSB1) plays a key role in . hSSB1 is a 211-residue polypeptide containing an oligonucleotide/oligosaccharide-binding (OB) fold at the N terminus. Following DNA damage, hSSB1 quickly relocates to DNA damage sites and regulates foci formation of other DNA damage repair proteins, such as BRCA1 and RAD51 (17,(21)(22)(23)(24). Thus, depletion of hSSB1 impairs the repair of DSBs. In response to DNA damage, hSSB1 is phosphorylated by ATM and regulates ATM-dependent cell cycle checkpoint activation (17,(21)(22)(23)(24). By protein affinity purifications, hSSB1 was shown to tightly associate with other proteins, such as INTS3, forming a multisubunit complex (21-24). INTS3 is a well-folded protein and previously identified as a member in the INTS complex that regulates RNA processing and gene transcription (25). Like hSSB1, INTS3 is also quickly relocated to DNA lesions in r...

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Section: Ints3supporting

confidence: 59%

mentioning

confidence: 84%

The oligonucleotide/oligosaccharide-binding fold motif is a poly(ADP-ribose)-binding domain that mediates DNA damage response

Zhang

Chen

et al. 2014

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

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“…However, based on the peptide screening, not all of the FHA and BRCT domains have high affinity to phospho-proteins (Durocher et al 2000;Rodriguez et al 2003). In particularly, our recent study suggests that the BARD1 BRCT domain recognizes ADP-ribose (Baer 2013;Li and Yu 2013). Thus, we asked whether these domains have other binding partners besides phospho-proteins.…”

mentioning

confidence: 99%

The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response

et al. 2013

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Poly-ADP-ribosylation is a unique post-translational modification participating in many biological processes, such as DNA damage response. Here, we demonstrate that a set of Forkhead-associated (FHA) and BRCA1 C-terminal (BRCT) domains recognizes poly(ADP-ribose) (PAR) both in vitro and in vivo. Among these FHA and BRCT domains, the FHA domains of APTX and PNKP interact with iso-ADP-ribose, the linkage of PAR, whereas the BRCT domains of Ligase4, XRCC1, and NBS1 recognize ADP-ribose, the basic unit of PAR. The interactions between PAR and the FHA or BRCT domains mediate the relocation of these domain-containing proteins to DNA damage sites and facilitate the DNA damage response. Moreover, the interaction between PAR and the NBS1 BRCT domain is important for the early activation of ATM during DNA damage response and ATM-dependent cell cycle checkpoint activation. Taken together, our results demonstrate two novel PAR-binding modules that play important roles in DNA damage response.

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“…Chromatin relaxation allows access to DNA repair factors, some of which are recruited through binding PAR. PARP1 mediates the initial accumulation of MRE11–RAD50–NBS1 (MRN) complex at DNA lesions and promotes rapid recruitment of BRCA1, BRCA2 and EXO1 involved in homologous recombination [26–29]. PAR also promotes recruitment of XRCC1 as a scaffold protein in base excision repair [17,30,31] and XPA as a scaffold protein in nucleotide excision repair [32].…”

Section: Introductionmentioning

confidence: 99%

“…By cleaving PAR, PARG promotes timely protein dissociation from DNA damage sites, as shown in the case of BRCA1, XRCC1, CHD2 and TRIM33 [25,26,43,44]. …”

Section: Introductionmentioning

confidence: 99%

Simultaneous dual-channel imaging to quantify interdependent protein recruitment to laser-induced DNA damage sites

Garbrecht

Hornegger

Herbert

et al. 2018

Nucleus

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Fluorescence microscopy in combination with the induction of localized DNA damage using focused light beams has played a major role in the study of protein recruitment kinetics to DNA damage sites in recent years. Currently published methods are dedicated to the study of single fluorophore/single protein kinetics. However, these methods may be limited when studying the relative recruitment dynamics between two or more proteins due to cell-to-cell variability in gene expression and recruitment kinetics, and are not suitable for comparative analysis of fast-recruiting proteins. To tackle these limitations, we have established a time-lapse fluorescence microscopy method based on simultaneous dual-channel acquisition following UV-A-induced local DNA damage coupled with a standardized image and recruitment analysis workflow. Simultaneous acquisition is achieved by spectrally splitting the emitted light into two light paths, which are simultaneously imaged on two halves of the same camera chip. To validate this method, we studied the recruitment of poly(ADP-ribose) polymerase 1 (PARP1), poly (ADP-ribose) glycohydrolase (PARG), proliferating cell nuclear antigen (PCNA) and the chromatin remodeler ALC1. In accordance with the published data based on single fluorophore imaging, simultaneous dual-channel imaging revealed that PARP1 regulates fast recruitment and dissociation of PARG and that in PARP1-depleted cells PARG and PCNA are recruited with comparable kinetics. This approach is particularly advantageous for analyzing the recruitment sequence of fast-recruiting proteins such as PARP1 and ALC1, and revealed that PARP1 is recruited faster than ALC1. Split-view imaging can be incorporated into any laser microirradiation-adapted microscopy setup together with a recruitment-dedicated image analysis package.

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Function of BRCA1 in the DNA Damage Response Is Mediated by ADP-Ribosylation

Cited by 278 publications

References 71 publications

The oligonucleotide/oligosaccharide-binding fold motif is a poly(ADP-ribose)-binding domain that mediates DNA damage response

The oligonucleotide/oligosaccharide-binding fold motif is a poly(ADP-ribose)-binding domain that mediates DNA damage response

The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response

Simultaneous dual-channel imaging to quantify interdependent protein recruitment to laser-induced DNA damage sites

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