Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2

Dray, Eloïse; Etchin, Julia; Wiese, Claudia; Saro, Dorina; Williams, Gareth J.; Hammel, Michal; Xiong, Yong; Galkin, Vitold E.; Liu, Dongqing; Tsai, Miaw-Sheue; Sy, Shirley M.-H.; Schild, David; Egelman, Edward H.; Chen, Junjie; Sung, Patrick

doi:10.1038/nsmb.1916

Cited by 144 publications

(156 citation statements)

References 23 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…Together with BRCA2, the PALB2-BRCA2 heterodimeric complex initiates high-fidelity homologous recombination (HR) 4 DNA repair by promoting the assimilation of the recombinase RAD51 onto resected 3Ј single-strand overhangs (1)(2)(3). Inactivation of PALB2 compromised RAD51 loading onto DNA breaks, greatly diminished HR repair, and hyper-sensitized cells to genotoxic stress (4,5).…”

mentioning

confidence: 99%

ATM-dependent Phosphorylation of the Fanconi Anemia Protein PALB2 Promotes the DNA Damage Response

Guo

Feng

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

ATM-dependent Phosphorylation of the Fanconi Anemia Protein PALB2 Promotes the DNA Damage Response

Guo

Feng

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…RAD51 is the central recombinase in HR, and it participates in D-loop formation and strand displacement (2). PALB2 also plays a BRCA2-independent role in the HR process by enhancing RAD51 function (3,4).…”

mentioning

confidence: 99%

Palb2 synergizes with Trp53 to suppress mammary tumor formation in a model of inherited breast cancer

Bowman-Colin

Xia

Bunting

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Germ-line mutations in PALB2 lead to a familial predisposition to breast and pancreatic cancer or to Fanconi Anemia subtype N. PALB2 performs its tumor suppressor role, at least in part, by supporting homologous recombination-type double strand break repair (HR-DSBR) through physical interactions with BRCA1, BRCA2, and RAD51. To further understand the mechanisms underlying PALB2-mediated DNA repair and tumor suppression functions, we targeted Palb2 in the mouse. Palb2-deficient murine ES cells recapitulated DNA damage defects caused by PALB2 depletion in human cells, and germline deletion of Palb2 led to early embryonic lethality. Somatic deletion of Palb2 driven by K14-Cre led to mammary tumor formation with long latency. Codeletion of both Palb2 and Tumor protein 53 (Trp53) accelerated mammary tumor formation. Like BRCA1 and BRCA2 mutant breast cancers, these tumors were defective in RAD51 focus formation, reflecting a defect in Palb2 HR-DSBR function, a strongly suspected contributor to Brca1, Brca2, and Palb2 mammary tumor development. However, unlike the case of Brca1-mutant cells, Trp53bp1 deletion failed to rescue the genomic instability of Palb2-or Brca2-mutant primary lymphocytes. Therefore, Palb2-driven DNA damage control is, in part, distinct from that executed by Brca1 and more similar to that of Brca2. The mechanisms underlying Palb2 mammary tumor suppression functions can now be explored genetically in vivo.mouse model | familial breast cancer

show abstract

“…3). Other biochemical studies showed that PALB2 binds DNA via two separate regions in the N-terminus of the protein, called PALB2 truncation 1 (P2T1) and PALB2 truncation 3 (P2T3), respectively (29,30). Particularly, P2T3 contains an evolutionarily conserved PALB2 motif, named chromatin-association motif (ChAM), which is figure 2.…”

Section: Discussionmentioning

confidence: 99%

A novel PALB2 truncating mutation in an Italian family with male breast cancer

et al. 2014

View full text Add to dashboard Cite

Abstract. Male breast cancer (MBC) is a rare disease, accounting for ~1% of all breast cancer cases worldwide. Although other genes are also involved, predisposing genetic factors to MBC include germline mutations in the BRCA genes (BRCA2). Among the other genes, partner and localizer of BRCA2 (PALB2) is considered a moderate-penetrance breast cancer susceptibility gene that may also play a role in MBC predisposition. Thus, the aim of the present study was to determine the PALB2 gene status in 8 MBC cases selected from a cohort of 181 hereditary breast and/or ovarian cancer probands. We performed PALB2 mutational analysis by direct sequencing of 13 exons and adjacent intronic regions. This study showed the presence of a PALB2 truncating mutation in 1/8 (12.5%) cases. This novel mutation was named c.1285_1286delAinsTC (p.I429SfsX12) and is localized in exon 4 of PALB2, in the region encoding for the ChAM motif which is important for the efficient association of PALB2 to chromatin and for recruitment of the BRCA complex to accumulate RAD51 at double-strand break sites. Our findings indicate that PALB2 could be added to the list of breast cancer susceptibility genes also in families with MBC cases.

show abstract

Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2

Cited by 144 publications

References 23 publications

ATM-dependent Phosphorylation of the Fanconi Anemia Protein PALB2 Promotes the DNA Damage Response

ATM-dependent Phosphorylation of the Fanconi Anemia Protein PALB2 Promotes the DNA Damage Response

Palb2 synergizes with Trp53 to suppress mammary tumor formation in a model of inherited breast cancer

A novel PALB2 truncating mutation in an Italian family with male breast cancer

Contact Info

Product

Resources

About