BRCA2 has an essential function in DNA repair by homologous recombination, interacting with RAD51 via short motifs in the middle and at the C terminus of BRCA2. Here, we report that a conserved 36-residue sequence of human BRCA2 encoded by exon 27 (BRCA2Exon27) interacts with RAD51 through the specific recognition of oligomerized RAD51 ATPase domains. BRCA2Exon27 binding stabilizes the RAD51 nucleoprotein filament against disassembly by BRC repeat 4. The protection is specific for RAD51 filaments formed on single-stranded DNA and is lost when BRCA2Exon27 is phosphorylated on Ser3291. We propose that productive recombination results from the functional balance between the different RAD51-binding modes [corrected] of the BRC repeat and exon 27 regions of BRCA2. Our results further suggest a mechanism in which CDK phosphorylation of BRCA2Exon27 at the G2-M transition alters the balance in favor of RAD51 filament disassembly, thus terminating recombination.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2096194 | PMC |
| http://dx.doi.org/10.1038/nsmb1251 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ecdysone and gene expressions for chromatin remodeling, histone modification, and Broad Complex in relation to pupal commitment in Bombyx mori.
Arch Insect Biochem Physiol
January 2024
Department of Bioproductive Science, Faculty of Agriculture, Takasaki University of Health and Welfare, Gunma, Japan.
In the present study, we tried to clarify when and how pupal commitment (PT) better to use PC occurs and what is involved in the PT of Bombyx mori. To clarify this, we examined the responsiveness of a wing disc to ecdysone, referring to metamorphosis-related BR-C, development-related Myc and Wnt, and chromatin remodeling-related genes at around the predicted PT stage of the Bombyx wing disc. Wing disc responsiveness to juvenile hormone (JH) and ecdysone was examined using Methoprene and 20-hydroxyecdysone (20E) in vitro.
View Article and Find Full Text PDFMultiomics data integration to reveal chromatin remodeling and reorganization induced by gene mutational synergy.
STAR Protoc
December 2022
Department of Haematology, University of Cambridge, Cambridge, UK; Wellcome - MRC Cambridge Stem Cell Institute, Cambridge, UK. Electronic address:
Recurrent gene mutations often cooperate in a predefined stepwise and synergistic manner to alter global transcription, through directly or indirectly remodeling epigenetic landscape on linear and three-dimensional (3D) scales. Here, we present a multiomics data integration approach to investigate the impact of gene mutational synergy on transcription, chromatin states, and 3D chromatin organization in a murine leukemia model. This protocol provides an executable framework to study epigenetic remodeling induced by cooperating gene mutations and to identify the critical regulatory network involved.
View Article and Find Full Text PDFSMARCE1 deficiency generates a targetable mSWI/SNF dependency in clear cell meningioma.
Nat Genet
June 2022
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes establish and maintain chromatin accessibility and gene expression, and are frequently perturbed in cancer. Clear cell meningioma (CCM), an aggressive tumor of the central nervous system, is uniformly driven by loss of SMARCE1, an integral subunit of the mSWI/SNF core. Here, we identify a structural role for SMARCE1 in selectively stabilizing the canonical BAF (cBAF) complex core-ATPase module interaction.
View Article and Find Full Text PDFOverarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology.
Nat Commun
May 2021
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one of its least studied members. We discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types.
View Article and Find Full Text PDFAge-associated proinflammatory elastic fiber remodeling in large arteries.
Mech Ageing Dev
June 2021
Laboratory of Cardiovascular Science, Intramural Research Program, National Institution on Aging, National Institutes of Health, Biomedical Research Center (BRC), 251 Bayview Boulevard, Baltimore, MD, 21224, USA. Electronic address:
Elastic fibers are the main components of the extracellular matrix of the large arterial wall. Elastic fiber remodeling is an intricate process of synthesis and degradation of the core elastin protein and microfibrils accompanied by the assembly and disassembly of accessory proteins. Age-related morphological, structural, and functional proinflammatory remodeling within the elastic fiber has a profound effect upon the integrity, elasticity, calcification, amyloidosis, and stiffness of the large arterial wall.
View Article and Find Full Text PDFWant 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!