Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Inheritance of Chromatin Structures

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...

Cell Specific Gene Expression

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...

Combinatorial Gene Control

Combinatorial Gene Control

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...

Chromatin Immunoprecipitation- ChIP

Chromatin Immunoprecipitation- ChIP

Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...

Treatment Resistant Cancers

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Mapping the genetic landscape of the DNA damage response with Cas12a-based combinatorial knockout screens.

bioRxiv : the preprint server for biology·2026

Same author

Replication stress primes a trophectoderm fate in embryonic stem cells.

Cell death discovery·2026

Same author

The DNA helicase HELQ promotes replication fork reversal in coordination with BRCA2- and FANCD2-mediated repair pathways.

Nucleic acids research·2026

Same author

Replicative gaps in DNA damage tolerance, genome instability, and cancer therapy.

Molecular cell·2026

Same author

Publisher Correction: Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome.

Nature communications·2026

Same author

An SP110-SP100 axis is a critical regulator of promyelocytic leukaemia body dynamics and mitotic fidelity.

Nature cell biology·2026

Search research articles

Related Experiment Video

Updated: Jun 22, 2026

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Published on: January 20, 2016

Chromatin determinants impart camptothecin sensitivity.

Fabio Puddu¹, Israel Salguero², Mareike Herzog^2,3

¹The Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge, UK f.puddu@gurdon.cam.ac.uk s.jackson@gurdon.cam.ac.uk.

|April 9, 2017

Summary

This summary is machine-generated.

Histone H4 K16 deacetylation increases sensitivity to camptothecin, a topoisomerase 1 inhibitor. Suppressing this deacetylation pathway rescues hypersensitivity in yeast lacking the Tof1/Csm3 complex.

Keywords:

H4‐K16 SIR complex Tof1 camptothecin synthetic viability

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Related Experiment Videos

Last Updated: Jun 22, 2026

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Published on: January 20, 2016

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Area of Science:

Molecular Biology
Genetics
Biochemistry

Background:

Camptothecin inhibits topoisomerase 1, causing DNA replication stress and topological challenges.
The Tof1/Csm3 complex is crucial for managing replication fork progression and preventing DNA catenation.

Purpose of the Study:

To investigate the genetic pathways conferring sensitivity to camptothecin.
To identify mechanisms that suppress camptothecin hypersensitivity, particularly in the absence of the Tof1/Csm3 complex.

Main Methods:

Synthetic viability screening in yeast to identify suppressors of camptothecin hypersensitivity.
Genetic analysis of histone modifications and chromatin domains, including H4 K16 acetylation and Sir1-dependent silencing.
Assessing the impact of mutations on camptothecin sensitivity and DNA catenation.

Main Results:

Histone H4 K16 deacetylation was identified as a key driver of camptothecin sensitivity.
Mutations inactivating H4 K16 deacetylation or the SIR1-4 genes significantly suppressed camptothecin hypersensitivity in tof1∆ strains.
Disruption of Sir1-dependent chromatin domains, but not rDNA or telomeric silencing, suppressed camptothecin sensitivity.

Conclusions:

Topoisomerase 1 inhibition near Sir1-dependent chromatin domains induces topological stress and DNA hypercatenation, especially when the Tof1/Csm3 complex is absent.
Histone H4 K16 deacetylation is a critical mediator of this sensitivity.
The identified mechanism is evolutionarily conserved.