Preserving genome integrity and function: the DNA damage response and histone modifications.

Crit Rev Biochem Mol Biol

Department of Molecular Biosciences, LIVESTRONG Cancer Institute of the Dell Medical School, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin , TX , USA.

Published: June 2019

Modulation of chromatin templates in response to cellular cues, including DNA damage, relies heavily on the post-translation modification of histones. Numerous types of histone modifications including phosphorylation, methylation, acetylation, and ubiquitylation occur on specific histone residues in response to DNA damage. These histone marks regulate both the structure and function of chromatin, allowing for the transition between chromatin states that function in undamaged condition to those that occur in the presence of DNA damage. Histone modifications play well-recognized roles in sensing, processing, and repairing damaged DNA to ensure the integrity of genetic information and cellular homeostasis. This review highlights our current understanding of histone modifications as they relate to DNA damage responses (DDRs) and their involvement in genome maintenance, including the potential targeting of histone modification regulators in cancer, a disease that exhibits both epigenetic dysregulation and intrinsic DNA damage.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715524PMC
http://dx.doi.org/10.1080/10409238.2019.1620676DOI Listing

Publication Analysis

Top Keywords

dna damage
24
histone modifications
16
damage histone
8
dna
7
histone
7
damage
6
preserving genome
4
genome integrity
4
integrity function
4
function dna
4

Similar Publications

Purpose: Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs).

Materials And Methods: Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database.

View Article and Find Full Text PDF

Optimized protocol for single-cell isolation and alkaline comet assay to detect DNA damage in cells of Drosophila wing imaginal discs.

STAR Protoc

January 2025

Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, TN, Italy; Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA. Electronic address:

Reduced expression of nucleolar genes induces stress and DNA damage. Here, we present a protocol to analyze DNA fragmentation at the single-cell level in Drosophila imaginal discs using an optimized alkaline comet assay. We describe steps for larvae development, tissue disaggregation, and single-cell dissociation.

View Article and Find Full Text PDF

Neutral lipids restrict the mobility of broken DNA molecules during comet assays.

Biol Cell

January 2025

Centre de Recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier, Centre National de la Recherche Scientifique, Montpellier, France.

One widespread technique to assess in relative terms the amount of broken DNA present in the genome of individual cells consists of immobilizing the cell's nucleus under an agarose pad (called the nucleoid) and subjecting the whole genome to electrophoresis to force broken DNA molecules out of it. Since the migrating broken DNA molecules create a tail behind the nucleoid, this technique is named the comet assay. While performing comet assays regularly, we systematically observed circular regions devoid of DNA within the nucleoid region.

View Article and Find Full Text PDF

WFDC3 sensitizes colorectal cancer to chemotherapy by regulating ATM/ATR kinase signaling pathway.

FASEB J

January 2025

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing, China.

Chemoresistance is an ongoing challenge for colorectal cancer (CRC) that significantly compromises the anti-tumor efficacy of current drugs. Identifying effective targets or drugs for overcoming chemoresistance is urgently needed. Our previous study showed that WFDC3 served as a tumor suppressor that hindered CRC metastasis.

View Article and Find Full Text PDF

The Potential Role of Sanguinarine as an Inhibitor of Leishmania PP2C in the Induction of Apoptosis.

Acta Parasitol

January 2025

División de Investigación, Facultad de Medicina, Unidad de Investigación UNAM-INC, Universidad Nacional Autónoma de México, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Ciudad de México, C.P. 14080, México.

Leishmania spp. cause a wide range of human diseases, localized skin lesions, mucocutaneous and visceral infections. In the present study, the aim was to investigate the potential role of sanguinarine as a specific inhibitor of Leishmania PP2C that can induce apoptosis in the parasite.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!