98%
921
2 minutes
20
The tumor suppressor BRCA2 is essential for homologous recombination (HR), replication fork stability, and DNA interstrand crosslink repair in vertebrates. We identify HSF2BP, a protein previously described as testis specific and not characterized functionally, as an interactor of BRCA2 in mouse embryonic stem cells, where the 2 proteins form a constitutive complex. HSF2BP is transcribed in all cultured human cancer cell lines tested and elevated in some tumor samples. Inactivation of the mouse Hsf2bp gene results in male infertility due to a severe HR defect during spermatogenesis. The BRCA2-HSF2BP interaction is highly evolutionarily conserved and maps to armadillo repeats in HSF2BP and a 68-amino acid region between the BRC repeats and the DNA binding domain of human BRCA2 (Gly2270-Thr2337) encoded by exons 12 and 13. This region of BRCA2 does not harbor known cancer-associated missense mutations and may be involved in the reproductive rather than the tumor-suppressing function of BRCA2.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.celrep.2019.05.096 | DOI Listing |
ESMO Open
September 2025
Division of Medical Oncology, Huntsman Cancer Institute, Salt Lake City, USA.
Background: Alterations in DNA damage repair (DDR) pathway genes can be exploited by cytotoxic chemotherapy regimens that induce DNA damage. Platinum chemotherapy has been shown to be particularly effective in DDR-mutated populations. However, the clinical impact of DDR mutations in metastatic colorectal cancer is still unknown.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Cancer Research Center of Marseille: Team DNA Damage and Genome Instability|CNRS, Inserm, Institut Paoli-Calmettes, Aix Marseille Université, Marseille 13009, France.
Following encounter with an unrepaired DNA lesion, replication is halted and can restart downstream of the lesion leading to the formation of a single-stranded DNA (ssDNA) gap. To complete replication, this ssDNA gap is filled in by one of the two lesion tolerance pathways: the error-prone Translesion Synthesis (TLS) or the error-free Homology Directed Gap Repair (HDGR). In the present work, we evidence a role for the RecBC complex distinct from its canonical function in homologous recombination at DNA double strand breaks.
View Article and Find Full Text PDFJ Hum Genet
September 2025
Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Comprehensive genomic profiling (CGP) expands treatment options for solid tumor patients and identifies hereditary cancers. However, in Japan, confirmatory tests have been conducted in only 31.6% of patients with presumed germline pathogenic variants (GPVs) detected through tumor-only testing.
View Article and Find Full Text PDFExp Cell Res
September 2025
Cancer Biology Laboratory, Dept of Life Sciences, GITAM School of Sciences, GITAM (Deemed to be University), Visakhapatnam, 530045, Andhra Pradesh, India. Electronic address:
CD151 is a tetraspanin, abnormally expressed in triple negative breast cancer (TNBC). It is a prominent component of exosomes, facilitating the secretion of proteins that promote metastasis and drug resistance. We have previously demonstrated that silencing the CD151 gene reduces metastasis in TNBC.
View Article and Find Full Text PDFNucleic Acids Res
September 2025
Université Paris-Saclay, INRAE, AgroParisTech, Institut Jean-Pierre Bourgin for Plant Sciences (IJPB), 78000 Versailles, France.
BRCA2 is crucial for mediating homology-directed DNA repair (HDR) through its binding to single-stranded DNA (ssDNA) and the recombinases RAD51 and DMC1. Most BRCA2 orthologs have a canonical DNA-binding domain (DBD) with the exception of Drosophila melanogaster. It remains unclear whether such a noncanonical BRCA2 variant without DBD possesses a DNA-binding activity.
View Article and Find Full Text PDF