Tripartite Motif-containing 33 (TRIM33) Protein Functions in the Poly(ADP-ribose) Polymerase (PARP)-dependent DNA Damage Response through Interaction with Amplified in Liver Cancer 1 (ALC1) Protein

Kulkarni, Atul; Oza, Jay; Yao, Ming; Sohail, Honeah; Ginjala, Vasudeva; Tomás-Loba, Antonia; Hořejšı́, Zuzana; Tan, Antoinette R.; Boulton, Simon J.; Ganesan, Shridar

doi:10.1074/jbc.m113.459164

Cited by 60 publications

(70 citation statements)

References 51 publications

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“…Of note, CBX8 appears to be dependent upon TRIM33 expression, but not on ALC1, for its recruitment to DNA breaks, even though the localization of TRIM33 is dependent on ALC1 localization (47). One possible explanation is that with ALC1 knockdown, although TRIM33 localization is greatly diminished, enough TRIM33 is present to support CBX8 localization.…”

Section: Discussionmentioning

confidence: 78%

“…Loading of nascent PAR modifications onto chromatin leads to the recruitment of several chromatin remodeling enzymes, including ALC1 and ubiquitin ligases such as TRIM33, which contributes to dynamic local chromatin relaxation and allows for efficient repair (18,47,51). Here, we demonstrate that the polycomb factor, CBX8, plays a role in PARP-dependent DNA damage repair pathway.…”

Section: Discussionmentioning

confidence: 85%

“…Alternatively, it may be that CBX8 localization depends on some activity of TRIM33 that does not require TRIM33 localization at DNA breaks. Interestingly, unlike the interaction of TRIM33 with ALC1, which is only present after induction of DNA damage (47), the biochemical interaction of TRIM33 with CBX8 appears to be constitutive (Fig. 4I).…”

Section: Discussionmentioning

confidence: 99%

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A Novel Role of Chromodomain Protein CBX8 in DNA Damage Response

Oza

Ganguly

Kulkarni

et al. 2016

Journal of Biological Chemistry

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Induction of DNA damage induces a dynamic repair process involving DNA repair factors and epigenetic regulators. Chromatin alterations must occur for DNA repair factors to gain access to DNA lesions and restore original chromatin configuration to preserve the gene expression profile. We characterize the novel role of CBX8, a chromodomain-containing protein with established roles in epigenetic regulation in DNA damage response. CBX8 protein rapidly accumulates at the sites of DNA damage within 30 s and progresses to accumulate until 4 min before gradually dispersing back to its predamage distribution by 15 min. CBX8 recruitment to the sites of DNA damage is dependent upon PARP1 activation and not dependent on ATM activation. CBX8 biochemically interacts with TRIM33, and its recruitment to DNA damage is also dependent on the presence of TRIM33. Knockdown of CBX8 using siRNA significantly reduces the efficiency of both homologous and the other nonhomologous recombination, as well as increases sensitivity of cells to ionizing radiation. These findings demonstrate that CBX8 functions in the PARP-dependent DNA damage response partly through interaction with TRIM33 and is required for efficient DNA repair.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 85%

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A Novel Role of Chromodomain Protein CBX8 in DNA Damage Response

Oza

Ganguly

Kulkarni

et al. 2016

Journal of Biological Chemistry

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“…Heterogeneity may be partly due to variable expression levels. For example, overexpression of ALC1 was shown to prolongue its retention at damage sites compared to endogenous ALC1 [44]. Our data show some correlation between initial fluorescence intensity, as an indicator of protein expression levels, and the time of maximum recruitment, whereby lower initial intensity leads to faster recruitment.…”

Section: Discussionmentioning

confidence: 60%

“…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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Bromodomains and Their Pharmacological Inhibitors

et al. 2014

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Over 60 bromodomains belonging to proteins with very different functions have been identified in humans. Several of them interact with acetylated lysine residues, leading to the recruitment and stabilization of protein complexes. The bromodomain and extra-terminal domain (BET) proteins contain tandem bromodomains which bind to acetylated histones and are thereby implicated in a number of DNA-centered processes, including the regulation of gene expression. The recent identification of inhibitors of BET and non-BET bromodomains is one of the few examples in which effective blockade of a protein-protein interaction can be achieved with a small molecule. This has led to major strides in the understanding of the function of bromodomain-containing proteins and their involvement in diseases such as cancer and inflammation. Indeed, BET bromodomain inhibitors are now being clinically evaluated for the treatment of hematological tumors and have also been tested in clinical trials for the relatively rare BRD-NUT midline carcinoma. This review gives an overview of the newest developments in the field, with a focus on the biology of selected bromodomain proteins on the one hand, and on reported pharmacological inhibitors on the other, including recent examples from the patent literature.

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Tripartite Motif-containing 33 (TRIM33) Protein Functions in the Poly(ADP-ribose) Polymerase (PARP)-dependent DNA Damage Response through Interaction with Amplified in Liver Cancer 1 (ALC1) Protein

Cited by 60 publications

References 51 publications

A Novel Role of Chromodomain Protein CBX8 in DNA Damage Response

A Novel Role of Chromodomain Protein CBX8 in DNA Damage Response

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

Bromodomains and Their Pharmacological Inhibitors

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