Cited by 861DNA Repair MechanismsBRCA gene mutations in cancerPARP inhibition in cancer therapy

Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2

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Xia, Bing, Sheng, Qing, Nakanishi, Koji, Ohashi, Akihiro, Wu, Jianmin, Christ, Nicole, Liu, Xinggang, Jasin, Maria +2 more·2006·Molecular Cell

Abstract

BRCA2 mutations predispose carriers to breast and ovarian cancer and can also cause other cancers and Fanconi anemia. BRCA2 acts as a "caretaker" of genome integrity by enabling homologous recombination (HR)-based, error-free DNA double-strand break repair (DSBR) and intra-S phase DNA damage checkpoint control. Described here is the identification of PALB2, a BRCA2 binding protein. PALB2 colocalizes with BRCA2 in nuclear foci, promotes its localization and stability in key nuclear structures (e.g., chromatin and nuclear matrix), and enables its recombinational repair and checkpoint functions. In addition, multiple, germline BRCA2 missense mutations identified in breast cancer patients but of heretofore unknown biological/clinical consequence appear to disrupt PALB2 binding and disable BRCA2 HR/DSBR function. Thus, PALB2 licenses key cellular biochemical properties of BRCA2 and ensures its tumor suppression function.

Integrity signals

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Crossref · 10.1016/j.molcel.2006.05.022

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  • The DR-U2OS cell line used in the study carries one integrated copy of the DR-GFP reporter.

    “The DR-U2OS cell line containing a single integrated copy of the DR-GFP reporter was used46,47.”

    From BRCA1–BARD1 promotes RAD51-mediated homologous DNA pairing (2017) · cites this paper as [47]

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Authors
Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F. J., & Livingston, D. M.
Affiliations
  • Harvard University (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Mayo Clinic (US)
Corresponding author
Livingston, David M.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2006-06
Volume
22
Issue
6
Pages
719-729
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2034702779
Cited by
861
References
57
Citations by year
2026: 18 · 2025: 34 · 2024: 41 · 2023: 55 · 2022: 46 · 2021: 58 · 2020: 46 · 2019: 56 · 2018: 45 · 2017: 45 · 2016: 51 · 2015: 38 · 2014: 43 · 2013: 45 · 2012: 31
FWCI
15.62
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute
  • Human Frontier Science Program
  • California Breast Cancer Research Program
  • Novartis
  • Breast Cancer Research Foundation
  • Medical Research and Materiel Command
  • National Institutes of Health
  • American Cancer Society
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Keywords
BRCA2, PALB2, homologous recombination, DNA double-strand break repair, S-phase checkpoint, genome stability, tumor suppression, breast cancer, ovarian cancer, Fanconi anemia, protein-protein interaction, nuclear foci, chromatin, nuclear matrix
MeSH terms
Fanconi Anemia Complementation Group N Protein, Breast Neoplasms, Chromatin, DNA Damage, DNA Repair, Female, HeLa Cells, Humans, Nuclear Proteins, Ovarian Neoplasms, Protein Binding, Recombination, Genetic, Nuclear Matrix, S Phase, Germ-Line Mutation, Genetic Predisposition to Disease, Mutation, Missense, BRCA2 Protein, Tumor Suppressor Proteins

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