MRGBP, a member of the NuA4 complex, inhibits DNA double-strand break repair.

FEBS Open Bio

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Spain.

Published: March 2021

The repair of DNA breaks takes place in the context of chromatin and thus involves the activity of chromatin remodelers. The nucleosome acetyltransferase of H4 (NuA4) remodeler complex enables DNA break repair by relaxing flanking chromatin. Here, we show that MRG domain binding protein (MRGBP), a member of this complex, acts as a general inhibitor of DNA double-strand break repair. Upon its downregulation, repair is generally increased. This is particularly evident for the stimulation of early events of homologous recombination. Thus, MRGBP has an opposing role to the main catalytic subunits of the NuA4 complex. Our data suggest that MRGBP acts by limiting the activity of this complex in DNA repair, specifically by narrowing the extent of DNA-end resection.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931222PMC
http://dx.doi.org/10.1002/2211-5463.13071DOI Listing

Publication Analysis

Top Keywords

break repair
12
mrgbp member
8
nua4 complex
8
dna double-strand
8
double-strand break
8
repair
6
complex
5
dna
5
mrgbp
4
member nua4
4

Similar Publications

Variants in the hereditary cancer-associated and genes can alter RNA splicing, producing transcripts that encode internally truncated yet potentially functional proteins. However, few studies have quantitatively analyzed variant-specific splicing isoforms. Here, we investigated cells heterozygous and homozygous for the :c.

View Article and Find Full Text PDF

Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data.

Nucleic Acids Res

December 2024

The David and Inez Myers Laboratory for Cancer Research,  Tel Aviv University, Tel Aviv 6997801, Israel.

Cellular senescence plays a significant role in tissue aging. Senescent cells, which resist apoptosis while remaining metabolically active, generate endogenous DNA-damaging agents, primarily reactive oxygen species. Efficient DNA repair is therefore crucial in these cells, especially when they undergo senescence escape, resuming DNA replication and cellular proliferation.

View Article and Find Full Text PDF

CHAMP1 premature termination codon mutations found in individuals with intellectual disability cause a homologous recombination defect through haploinsufficiency.

Sci Rep

December 2024

Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.

CHAMP1 (chromosome alignment-maintaining phosphoprotein 1) plays a role in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The CHAMP1 gene is one of the genes mutated in individuals with intellectual disability. The majority of the mutations are premature termination codon (PTC) mutations, while missense mutations have also been reported.

View Article and Find Full Text PDF

PARP1 inhibitor niraparib exerts synergistic antimyeloma effect with bortezomib through inducing DNA damage and inhibiting DNA repair.

Free Radic Biol Med

December 2024

Hematology Institute, School of Medicine, Northwest University, Xian 710069, Shaanxi, China; Deparment of Hematology, Affiliated Hospital of Northwest University & Xian No. 3 Hospital, Xian 710018, Shaanxi, China. Electronic address:

Despite the improvements in outcomes for patients with multiple myeloma (MM) over the past decade, the disease remains incurable, and even those patients who initially respond favorably to induction therapy eventually suffer from relapse. Consequently, there is an urgent need for the development of novel therapeutic agents and strategies to enhance the treatment outcomes for patients with MM. The proteasome inhibitor bortezomib (BTZ) elicits endoplasmic reticulum (ER) stress and oxidative stress in MM cells, subsequent DNA damage, ultimately inducing cell apoptosis.

View Article and Find Full Text PDF

Background: There is a growing interest in exploring the biological characteristics of nanoparticles and exploring their potential applications. However, there is still a lack of research into the potential genotoxicity of fullerene derivatives and their impact on gene expression in human cells. In this study, we investigated the effects of a water-soluble fullerene derivative, C60[C6H4SCH2COOK]5H (F1), on human embryonic lung fibroblasts (HELF).

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!