LIVIVO - Search results -

Search results

Result 1 - 10 of total 71

Article: BRCA1

Krishnan, Rehna / Patel, Parasvi S / Hakem, Razqallah

2021 Volume 14, Issue 1

Abstract: Heritable mutations ... ...

Abstract	Heritable mutations in
Language	English
Publishing date	2021-12-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14010108
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Emerging roles of DNA topoisomerases in the regulation of R-loops.

Patel, Parasvi S / Krishnan, Rehna / Hakem, Razqallah

Mutation research. Genetic toxicology and environmental mutagenesis

2022 Volume 876-877, Page(s) 503450

Abstract: R-loops are comprised of a DNA:RNA hybrid and a displaced single-strand DNA (ssDNA) that reinvades the DNA duplex behind the moving RNA polymerase. Because they have several physiological functions within the cell, including gene expression, chromosomal ... ...

Abstract	R-loops are comprised of a DNA:RNA hybrid and a displaced single-strand DNA (ssDNA) that reinvades the DNA duplex behind the moving RNA polymerase. Because they have several physiological functions within the cell, including gene expression, chromosomal segregation, and mitochondrial DNA replication, among others, R-loop homeostasis is tightly regulated to ensure normal functioning of cellular processes. Thus, several classes of enzymes including RNases, helicases, topoisomerases, as well as proteins involved in splicing and the biogenesis of messenger ribonucleoproteins, have been implicated in R-loop prevention, suppression, and resolution. There exist six topoisomerase enzymes encoded by the human genome that function to introduce transient DNA breaks to relax supercoiled DNA. In this mini-review, we discuss functions of DNA topoisomerases and their emerging role in transcription, replication, and regulation of R-loops, and we highlight how their role in maintaining genome stability can be exploited for cancer therapy.
MeSH term(s)	DNA/genetics ; DNA Replication ; DNA Topoisomerases/genetics ; Genomic Instability ; Humans ; R-Loop Structures
Chemical Substances	DNA (9007-49-2) ; DNA Topoisomerases (EC 5.99.1.-)
Language	English
Publishing date	2022-01-20
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	1879-3592
ISSN (online)	1879-3592
DOI	10.1016/j.mrgentox.2022.503450
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: DNA double-strand break-capturing nuclear envelope tubules drive DNA repair.

Shokrollahi, Mitra / Stanic, Mia / Hundal, Anisha / Chan, Janet N Y / Urman, Defne / Jordan, Chris A / Hakem, Anne / Espin, Roderic / Hao, Jun / Krishnan, Rehna / Maass, Philipp G / Dickson, Brendan C / Hande, Manoor P / Pujana, Miquel A / Hakem, Razqallah / Mekhail, Karim

Nature structural & molecular biology

2024

Abstract: Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner ... ...

Abstract	Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner depending on DNA damage response (DDR) kinases and cytoplasmic microtubules acetylated by α-tubulin acetyltransferase-1 (ATAT1). These factors collaborate with the linker of nucleoskeleton and cytoskeleton complex (LINC), nuclear pore complex (NPC) protein NUP153, nuclear lamina and kinesins KIF5B and KIF13B to generate DSB-capturing nuclear envelope tubules (dsbNETs). dsbNETs are partly supported by nuclear actin filaments and the circadian factor PER1 and reversed by kinesin KIFC3. Although dsbNETs promote repair and survival, they are also co-opted during poly(ADP-ribose) polymerase (PARP) inhibition to restrain BRCA1-deficient breast cancer cells and are hyper-induced in cells expressing the aging-linked lamin A mutant progerin. In summary, our results advance understanding of nuclear structure-function relationships, uncover a nuclear-cytoplasmic DDR and identify dsbNETs as critical factors in genome organization and stability.
Language	English
Publishing date	2024-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2126708-X
ISSN	1545-9985 ; 1545-9993
ISSN (online)	1545-9985
ISSN	1545-9993
DOI	10.1038/s41594-024-01286-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4101: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 56: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: SARS-CoV-2 targets ribosomal RNA biogenesis.

Yerlici, V Talya / Astori, Audrey / Kejiou, Nevraj S / Jordan, Chris A / Khosraviani, Negin / Chan, Janet N Y / Hakem, Razqallah / Raught, Brian / Palazzo, Alexander F / Mekhail, Karim

Cell reports

2024 Volume 43, Issue 3, Page(s) 113891

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hinders host gene expression, curbing defenses and licensing viral protein synthesis and virulence. During SARS-CoV-2 infection, the virulence factor non-structural protein 1 (Nsp1) targets the ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hinders host gene expression, curbing defenses and licensing viral protein synthesis and virulence. During SARS-CoV-2 infection, the virulence factor non-structural protein 1 (Nsp1) targets the mRNA entry channel of mature cytoplasmic ribosomes, limiting translation. We show that Nsp1 also restrains translation by targeting nucleolar ribosome biogenesis. SARS-CoV-2 infection disrupts 18S and 28S ribosomal RNA (rRNA) processing. Expression of Nsp1 recapitulates the processing defects. Nsp1 abrogates rRNA production without altering the expression of critical processing factors or nucleolar organization. Instead, Nsp1 localizes to the nucleolus, interacting with precursor-rRNA and hindering its maturation separately from the viral protein's role in restricting mature ribosomes. Thus, SARS-CoV-2 Nsp1 limits translation by targeting ribosome biogenesis and mature ribosomes. These findings revise our understanding of how SARS-CoV-2 Nsp1 controls human protein synthesis, suggesting that efforts to counter Nsp1's effect on translation should consider the protein's impact from ribosome manufacturing to mature ribosomes.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; RNA, Ribosomal/metabolism ; COVID-19/metabolism ; Ribosomes/metabolism ; Viral Proteins/metabolism ; Viral Nonstructural Proteins/metabolism
Chemical Substances	RNA, Ribosomal ; Viral Proteins ; Viral Nonstructural Proteins
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2024.113891
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: DNA-damage repair; the good, the bad, and the ugly.

Hakem, Razqallah

The EMBO journal

2008 Volume 27, Issue 4, Page(s) 589–605

Abstract: Organisms have developed several DNA-repair pathways as well as DNA-damage checkpoints to cope with the frequent challenge of endogenous and exogenous DNA insults. In the absence or impairment of such repair or checkpoint mechanisms, the genomic ... ...

Abstract	Organisms have developed several DNA-repair pathways as well as DNA-damage checkpoints to cope with the frequent challenge of endogenous and exogenous DNA insults. In the absence or impairment of such repair or checkpoint mechanisms, the genomic integrity of the organism is often compromised. This review will focus on the functional consequences of impaired DNA-repair pathways. Although each pathway is addressed individually, it is essential to note that cross talk exists between repair pathways, and that there are instances in which a DNA-repair protein is involved in more than one pathway. It is also important to integrate DNA-repair process with DNA-damage checkpoints and cell survival, to gain a better understanding of the consequences of compromised DNA repair at both cellular and organismic levels. Functional consequences associated with impaired DNA repair include embryonic lethality, shortened life span, rapid ageing, impaired growth, and a variety of syndromes, including a pronounced manifestation of cancer.
MeSH term(s)	Animals ; DNA Damage ; DNA Repair ; DNA-Binding Proteins/metabolism ; Humans
Chemical Substances	DNA-Binding Proteins
Language	English
Publishing date	2008-02-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.1038/emboj.2008.15
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1808: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 100: Show issues

Order via subito

Details ▾

Article ; Online: Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers.

Nucleic acids research

2023 Volume 51, Issue 9, Page(s) 4341–4362

Abstract: BRCA1 mutations are associated with increased breast and ovarian cancer risk. BRCA1-mutant tumors are high-grade, recurrent, and often become resistant to standard therapies. Herein, we performed a targeted CRISPR-Cas9 screen and identified MEPCE, a ... ...

Abstract	BRCA1 mutations are associated with increased breast and ovarian cancer risk. BRCA1-mutant tumors are high-grade, recurrent, and often become resistant to standard therapies. Herein, we performed a targeted CRISPR-Cas9 screen and identified MEPCE, a methylphosphate capping enzyme, as a synthetic lethal interactor of BRCA1. Mechanistically, we demonstrate that depletion of MEPCE in a BRCA1-deficient setting led to dysregulated RNA polymerase II (RNAPII) promoter-proximal pausing, R-loop accumulation, and replication stress, contributing to transcription-replication collisions. These collisions compromise genomic integrity resulting in loss of viability of BRCA1-deficient cells. We also extend these findings to another RNAPII-regulating factor, PAF1. This study identifies a new class of synthetic lethal partners of BRCA1 that exploit the RNAPII pausing regulation and highlight the untapped potential of transcription-replication collision-inducing factors as unique potential therapeutic targets for treating cancers associated with BRCA1 mutations.
MeSH term(s)	Humans ; BRCA1 Protein/deficiency ; BRCA1 Protein/genetics ; DNA Replication/genetics ; Hereditary Breast and Ovarian Cancer Syndrome/genetics ; Hereditary Breast and Ovarian Cancer Syndrome/pathology ; Hereditary Breast and Ovarian Cancer Syndrome/physiopathology ; Mutation ; RNA Polymerase II/metabolism ; Transcription, Genetic/genetics ; Promoter Regions, Genetic ; Methyltransferases/deficiency ; Methyltransferases/genetics ; R-Loop Structures ; Cell Death
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; PAF1 protein, human ; RNA Polymerase II (EC 2.7.7.-) ; MePCE protein, human (EC 2.1.1.-) ; Methyltransferases (EC 2.1.1.-)
Language	English
Publishing date	2023-03-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkad172
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1067: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: From photomorphogenesis to cancer: a CSN journey.

Salmena, Leonardo / Hakem, Razqallah

Cell cycle (Georgetown, Tex.)

2012 Volume 12, Issue 2, Page(s) 205–206

MeSH term(s)	Animals ; Cyclin-Dependent Kinase Inhibitor p57/metabolism ; Humans ; Multiprotein Complexes/metabolism ; Peptide Hydrolases/metabolism
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p57 ; Multiprotein Complexes ; Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2012-01-15
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.4161/cc.23422
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5881: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: LATS2 Suppresses Oncogenic Wnt Signaling by Disrupting β-Catenin/BCL9 Interaction.

Li, Jiong / Chen, Xiaohong / Ding, Xiangming / Cheng, Yingduan / Zhao, Bin / Lai, Zhi-Chun / Al Hezaimi, Khalid / Hakem, Razqallah / Guan, Kun-Liang / Wang, Cun-Yu

Cell reports

2020 Volume 31, Issue 11, Page(s) 107792

Language	English
Publishing date	2020-06-16
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.107792
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages.

Kim, Hyeyeon / Aliar, Kazeera / Tharmapalan, Pirashaanthy / McCloskey, Curtis W / Kuttanamkuzhi, Abhijith / Grünwald, Barbara T / Palomero, Luis / Mahendralingam, Mathepan J / Waas, Matthew / Mer, Arvind S / Elliott, Mitchell J / Zhang, Bowen / Al-Zahrani, Khalid N / Langille, Ellen R / Parsons, Michael / Narala, Swami / Hofer, Stefan / Waterhouse, Paul D / Hakem, Razqallah /

Haibe-Kains, Benjamin / Kislinger, Thomas / Schramek, Daniel / Cescon, David W / Pujana, Miquel A / Berman, Hal K / Khokha, Rama

Cell reports

2023 Volume 42, Issue 11, Page(s) 113382

Language	English
Publishing date	2023-10-25
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.113382
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Dual Role of Caspase 8 in Adipocyte Apoptosis and Metabolic Inflammation.

Luk, Cynthia T / Chan, Carmen K / Chiu, Felix / Shi, Sally Yu / Misra, Paraish S / Li, Yu Zhe / Pollock-Tahiri, Evan / Schroer, Stephanie A / Desai, Harsh R / Sivasubramaniyam, Tharini / Cai, Erica P / Krishnamurthy, Mansa / Han, Daniel J / Chowdhury, Apu / Aslam, Rukhsana / Yuen, Darren A / Hakem, Anne / Hakem, Razqallah / Woo, Minna

Diabetes

2023 Volume 72, Issue 12, Page(s) 1751–1765

Abstract: Caspases are cysteine-aspartic proteases that were initially discovered to play a role in apoptosis. However, caspase 8, in particular, also has additional nonapoptotic roles, such as in inflammation. Adipocyte cell death and inflammation are ... ...

Abstract	Caspases are cysteine-aspartic proteases that were initially discovered to play a role in apoptosis. However, caspase 8, in particular, also has additional nonapoptotic roles, such as in inflammation. Adipocyte cell death and inflammation are hypothesized to be initiating pathogenic factors in type 2 diabetes. Here, we examined the pleiotropic role of caspase 8 in adipocytes and obesity-associated insulin resistance. Caspase 8 expression was increased in adipocytes from mice and humans with obesity and insulin resistance. Treatment of 3T3-L1 adipocytes with caspase 8 inhibitor Z-IETD-FMK decreased both death receptor-mediated signaling and targets of nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling. We generated novel adipose tissue and adipocyte-specific caspase 8 knockout mice (aP2Casp8-/- and adipoqCasp8-/-). Both males and females had improved glucose tolerance in the setting of high-fat diet (HFD) feeding. Knockout mice also gained less weight on HFD, with decreased adiposity, adipocyte size, and hepatic steatosis. These mice had decreased adipose tissue inflammation and decreased activation of canonical and noncanonical NF-κB signaling. Furthermore, they demonstrated increased energy expenditure, core body temperature, and UCP1 expression. Adipocyte-specific activation of Ikbkb or housing mice at thermoneutrality attenuated improvements in glucose tolerance. These data demonstrate an important role for caspase 8 in mediating adipocyte cell death and inflammation to regulate glucose and energy homeostasis. Article highlights: Caspase 8 is increased in adipocytes from mice and humans with obesity and insulin resistance. Knockdown of caspase 8 in adipocytes protects mice from glucose intolerance and weight gain on a high-fat diet. Knockdown of caspase 8 decreases Fas signaling, as well as canonical and noncanonical nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling in adipose tissue. Improved glucose tolerance occurs via reduced activation of NF-κB signaling and via induction of UCP1 in adipocytes.
MeSH term(s)	Humans ; Male ; Female ; Animals ; Mice ; NF-kappa B/metabolism ; Insulin Resistance/genetics ; Caspase 8/genetics ; Caspase 8/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Mice, Knockout ; Adipocytes/metabolism ; Obesity/genetics ; Obesity/metabolism ; Diet, High-Fat/adverse effects ; Inflammation/metabolism ; Glucose/metabolism ; Apoptosis/genetics
Chemical Substances	NF-kappa B ; Caspase 8 (EC 3.4.22.-) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-09-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db22-1033
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.175: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito