BAL1 and Its Partner E3 Ligase, BBAP, Link Poly(ADP-Ribose) Activation, Ubiquitylation, and Double-Strand DNA Repair Independent of ATM, MDC1, and RNF8

Yan, Qingsheng; Xu, Rong; Zhu, Liya; Cheng, Xin; Wang, Zhe; Manis, John P.; Shipp, Margaret A.

doi:10.1128/mcb.00990-12

Cited by 94 publications

(119 citation statements)

References 32 publications

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“…In addition to their role at the DNA break sites, HDAC1,2 inhibition increases H3K27ac globally and at the promoters of DNA damage response genes, suggesting a role for HDAC1,2 in maintaining the H3K27ac-H3K27me3 balance within the cell. We also report that the EZH2 GOF DLBCL cells overexpress BBAP, (B-lymphoma and BAL-associated protein), an E3 ligase involved in monoubiquitination of histone H4K91 [15], a factor that was shown to be associated with chemoresistance previously [16-18]. Our findings show that H4K91ac is a novel target of HDAC1,2.…”

Section: Introductionsupporting

confidence: 54%

HDAC1,2 inhibition impairs EZH2- and BBAP- mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma

et al. 2014

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Gain-of-function mutations in the catalytic site of EZH2 (Enhancer of Zeste Homologue 2), is observed in about 22% of diffuse large B-cell lymphoma (DLBCL) cases. Here we show that selective inhibition of histone deacetylase 1,2 (HDAC1,2) activity using a small molecule inhibitor causes cytotoxic or cytostatic effects in EZH2 gain-of-function mutant (EZH2GOF) DLBCL cells. Our results show that blocking the activity of HDAC1,2 increases global H3K27ac without causing a concomitant global decrease in H3K27me3 levels. Our data shows that inhibition of HDAC1,2 is sufficient to decrease H3K27me3 present at DSBs, decrease DSB repair and activate the DNA damage response in these cells. In addition to increased H3K27me3, we found that the EZH2GOF DLBCL cells overexpress another chemotherapy resistance factor − B-lymphoma and BAL-associated protein (BBAP). BBAP monoubiquitinates histone H4K91, a residue that is also subjected to acetylation. Our results show that selective inhibition of HDAC1,2 increases H4K91ac, decreases BBAP-mediated H4K91 monoubiquitination, impairs BBAP-dependent DSB repair and sensitizes the refractory EZH2GOF DLBCL cells to treatment with doxorubicin, a chemotherapy agent. Hence, selective HDAC1,2 inhibition provides a novel DNA repair mechanism-based therapeutic approach as it can overcome both EZH2- and BBAP-mediated DSB repair in the EZH2GOF DLBCL cells.

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Section: Introductionsupporting

confidence: 54%

HDAC1,2 inhibition impairs EZH2- and BBAP- mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma

et al. 2014

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“…PARP9 and DTXL3, two key regulators of PARP1 DNA damage response [46,47], had lower expression levels in FXN cDNA treated cells than in control cells. Thus FXN may play a role in interferon-induced apoptosis and DNA damage regulation in FRDA cells.…”

Section: Accepted Manuscriptmentioning

confidence: 70%

Characterization of frataxin gene network in Friedreich's ataxia fibroblasts using the RNA-Seq technique

et al. 2016

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“…Interestingly, our results are consistent with recent evidence showing that the depletion of MRE11, Nijmegen breakage syndrome 1, and chromodomain helicase DNA binding protein 4 (CHD4) proteins, whose recruitment to sites of DNA damage is regulated by PARP1, disrupts the HDR of DSB (47)(48)(49). Moreover, the rapid and transient recruitment of KDM4D to sites of DNA damage is in line with the increasing numbers of DDR proteins that show transient recruitment, but long lasting effect on repair and/or DNA damage-induced foci formation (49)(50)(51)(52)(53)(54)(55).…”

Section: Kdm4d Affects the Ir-induced Foci Formation Of Rad51 And 53bp1mentioning

confidence: 86%

PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair

Khoury-Haddad

Guttmann‐Raviv

Ipenberg

et al. 2014

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

125

162

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Members of the lysine (K)-specific demethylase 4 (KDM4) A-D family of histone demethylases are dysregulated in several types of cancer. Here, we reveal a previously unrecognized role of KDM4D in the DNA damage response (DDR). We show that the C-terminal region of KDM4D mediates its rapid recruitment to DNA damage sites. Interestingly, this recruitment is independent of the DDR sensor ataxia telangiectasia mutated (ATM), but dependent on poly (ADP-ribose) polymerase 1 (PARP1), which ADP ribosylates KDM4D after damage. We demonstrate that KDM4D is required for efficient phosphorylation of a subset of ATM substrates. We note that KDM4D depletion impairs the DNA damage-induced association of ATM with chromatin, explaining its effect on ATM substrate phosphorylation. Consistent with an upstream role in DDR, KDM4D knockdown disrupts the damage-induced recombinase Rad51 and tumor protein P53 binding protein foci formation. Consequently, the integrity of homology-directed repair and nonhomologous end joining of DNA breaks is impaired in KDM4D-deficient cells. Altogether, our findings implicate KDM4D in DDR, furthering the links between the cancer-relevant networks of epigenetic regulation and genome stability.histone demethylation | chromosome instability | PARylation

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BAL1 and Its Partner E3 Ligase, BBAP, Link Poly(ADP-Ribose) Activation, Ubiquitylation, and Double-Strand DNA Repair Independent of ATM, MDC1, and RNF8

Cited by 94 publications

References 32 publications

HDAC1,2 inhibition impairs EZH2- and BBAP- mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma

HDAC1,2 inhibition impairs EZH2- and BBAP- mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma

Characterization of frataxin gene network in Friedreich's ataxia fibroblasts using the RNA-Seq technique

PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair

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