Role of deubiquitinases in DNA damage response

Le, John Philip; Perez, Éric; Nemzow, Leah; Gong, Feng

doi:10.1016/j.dnarep.2019.02.011

Cited by 19 publications

(9 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regulation of protein expression and posttranslational modifications in response to DNA damage are characteristics suggestive of DDR involvement 38–40 . CTDP1 expression across a panel of seven breast cell lines revealed that 5/6 cancer lines maintained their CTDP1 expression following ICL damage with melphalan (Fig.…”

Section: Resultsmentioning

confidence: 99%

CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI

Krieger

Lagundžin

et al. 2019

Cell Death Discov.

View full text Add to dashboard Cite

BRCA1 C-terminal domains are found in a specialized group of 23 proteins that function in the DNA damage response to protect genomic integrity. C-terminal domain phosphatase 1 (CTDP1) is the only phosphatase with a BRCA1 C-terminal domain in the human proteome, yet direct participation in the DNA damage response has not been reported. Examination of the CTDP1 BRCA1 C-terminal domain-specific protein interaction network revealed 103 high confidence interactions enriched in DNA damage response proteins, including FANCA and FANCI that are central to the Fanconi anemia DNA repair pathway necessary for the resolution of DNA interstrand crosslink damage. CTDP1 expression promotes DNA damage-induced FANCA and FANCD2 foci formation and enhances homologous recombination repair efficiency. CTDP1 was found to regulate multiple aspects of FANCI activity, including chromatin localization, interaction with γ-H2AX, and SQ motif phosphorylations. Knockdown of CTDP1 increases MCF-10A sensitivity to DNA interstrand crosslinks and double-strand breaks, but not ultraviolet radiation. In addition, CTDP1 knockdown impairs in vitro and in vivo growth of breast cancer cell lines. These results elucidate the molecular functions of CTDP1 in Fanconi anemia interstrand crosslink repair and identify this protein as a potential target for breast cancer therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI

Krieger

Lagundžin

et al. 2019

Cell Death Discov.

View full text Add to dashboard Cite

show abstract

“…20 ). Several DUBs have been reported to be related to the regulation of DDR activity [ 35 ]. USP14 regulates the DDR by targeting RNF168-dependent ubiquitination [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

USP24 promotes drug resistance during cancer therapy

et al. 2021

View full text Add to dashboard Cite

Drug resistance has remained an important issue in the treatment and prevention of various diseases, including cancer. Herein, we found that USP24 not only repressed DNA-damage repair (DDR) activity by decreasing Rad51 expression to cause the tumor genomic instability and cancer stemness, but also increased the levels of the ATP-binding cassette (ABC) transporters P-gp, ABCG2, and ezrin to enhance the pumping out of Taxol from cancer cells, thus resulted in drug resistance during cancer therapy. A novel USP24 inhibitor, NCI677397, was screened for specific inhibiting the catalytic activity of USP24. This inhibitor was identified to suppress drug resistance via decreasing genomic instability, cancer stemness, and the pumping out of drugs from cancer cells. Understanding the role and molecular mechanisms of USP24 in drug resistance will be beneficial for the future development of a novel USP24 inhibitor. Our studies provide a new insight of USP24 inhibitor for clinically implication of blocking drug resistance during chemotherapy.

show abstract

“…Our findings in human cancerous tissues suggest that SAMHD1 might be implicated in early-stage carcinomas to overcome elevated DNA damage and oncogenic stress. In eukaryotic cells, ubiquitination plays an essential role in the assembly as well as disassembly of DDR factors at break sites 30,31 . Both ROS and genotoxic insults, such as cisplatin or doxorubicin, may increase SAMHD1 by inducing its protein deubiquitination and promote the interaction of SAMHD1 with CtIP for DDR.…”

Section: Discussionmentioning

confidence: 99%

De-ubiquitination of SAMHD1 by USP7 overcomes oncogenic stress and contributes to chemotherapy insensitivity

Liu

Zhou²,

Dong³

et al. 2021

Preprint

View full text Add to dashboard Cite

Oncogenic stress induces DNA damage response (DDR) that guards against genetic instability during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in DNA damage repair process. However, its role in tumorigenesis remains largely unknown. Here, we show that SAMHD1 is up-regulated in early-stage human carcinoma tissues and cell lines under oxidative stress or genotoxic insults. We further demonstrate that de-ubiquitinating enzyme USP7 interacts with SAMHD1 and de-ubiquitinates it at lysine 421, thus stabilizing SAMHD1 protein expression, and promotes tumor cell survival under genotoxic stress. Furthermore, SAMHD1 levels positively correlates with USP7 in various human carcinomas, and is associated with an unfavorable survival outcome in patients who underwent chemotherapy. Moreover, USP7 inhibitor sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1 in vitro and in vivo. These findings suggest that targeting USP7 may help overcome chemoresistance, thus necessitating further investigation in the pursuit of precision medicine.

show abstract

Role of deubiquitinases in DNA damage response

Cited by 19 publications

References 124 publications

CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI

CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI

USP24 promotes drug resistance during cancer therapy

De-ubiquitination of SAMHD1 by USP7 overcomes oncogenic stress and contributes to chemotherapy insensitivity

Contact Info

Product

Resources

About