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Int. J. Mol. Sci. 2017, 18(9), 1886; doi:10.3390/ijms18091886

The Role of PALB2 in the DNA Damage Response and Cancer Predisposition

1
Programa de Pesquisa Clínica, Instituto Nacional de Câncer, Rio de Janeiro 20231-050, Brazil
2
Instituto de Biofísica Carlos Chagas Filho–Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-599, Brazil
3
Cancer Epidemiology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
4
Instituto Federal do Rio de Janeiro-IFRJ, Rio de Janeiro 20270-021, Brazil
*
Author to whom correspondence should be addressed.
Received: 28 July 2017 / Revised: 21 August 2017 / Accepted: 26 August 2017 / Published: 31 August 2017
(This article belongs to the Special Issue DNA Injury and Repair Systems)
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Abstract

The deoxyribonucleic acid (DNA) damage response (DDR) is a major feature in the maintenance of genome integrity and in the suppression of tumorigenesis. PALB2 (Partner and Localizer of Breast Cancer 2 (BRCA2)) plays an important role in maintaining genome integrity through its role in the Fanconi anemia (FA) and homologous recombination (HR) DNA repair pathways. Since its identification as a BRCA2 interacting partner, PALB2 has emerged as a pivotal tumor suppressor protein associated to hereditary cancer susceptibility to breast and pancreatic cancers. In this review, we discuss how other DDR proteins (such as the kinases Ataxia Telangiectasia Mutated (ATM) and ATM- and Rad3-Related (ATR), mediators BRCA1 (Breast Cancer 1)/BRCA2 and effectors RAD51/DNA Polymerase η (Polη) interact with PALB2 to orchestrate DNA repair. We also examine the involvement of PALB2 mutations in the predisposition to cancer and the role of PALB2 in stimulating error-free DNA repair through the FA/HR pathway. View Full-Text
Keywords: Breast Cancer 1 (BRCA1); Breast Cancer 2 (BRCA2); Partner and Localizer of BRCA2 (PALB2); Fanconi Anemia Group N protein (FANCN); cancer predisposition; deoxyribonucleic acid (DNA) damage response; DNA double strand break; Fanconi anemia; homologous recombination Breast Cancer 1 (BRCA1); Breast Cancer 2 (BRCA2); Partner and Localizer of BRCA2 (PALB2); Fanconi Anemia Group N protein (FANCN); cancer predisposition; deoxyribonucleic acid (DNA) damage response; DNA double strand break; Fanconi anemia; homologous recombination
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Nepomuceno, T.C.; De Gregoriis, G.; de Oliveira, F.M.B.; Suarez-Kurtz, G.; Monteiro, A.N.; Carvalho, M.A. The Role of PALB2 in the DNA Damage Response and Cancer Predisposition. Int. J. Mol. Sci. 2017, 18, 1886.

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