Abstract
Partner and localizer of BRCA2 (PALB2) is vital for homologous recombination (HR) repair in response to DNA double-strand breaks (DSBs). PALB2 functions as a tumor suppressor and participates in the maintenance of genome integrity. In this review, we summarize the current knowledge of the biological roles of the multifaceted PALB2 protein and of its regulation. Moreover, we describe the link between PALB2 pathogenic variants (PVs) and breast cancer predisposition, aggressive clinicopathological features, and adverse clinical prognosis. We also refer to both the opportunities and challenges that the identification of PALB2 PVs provides in breast cancer genetic counseling and precision medicine.
Highlights
Partner and localizer of BRCA2 (PALB2) is encoded on chromosome 16p12.2 and comprises 1186 residues [1]
A recent international study from 21 countries that comprised 524 families with PALB2 pathogenic variants (PVs) revealed that the estimated relative risk associated with PALB2 PVs for breast cancer in females was 7.18
The specific structures, multifaceted functions, and complex regulatory networks of PALB2 have been elaborated by multiple studies
Summary
Partner and localizer of BRCA2 (PALB2) is encoded on chromosome 16p12.2 and comprises 1186 residues [1]. In addition to BRCA complex formation, PALB2 directly interacts with RAD51 and enhances its strand invasion activity [24, 25]. In BRCA1 mutated cells, RNF168-mediated PALB2 recruitment plays a vital alternative role for RAD51 loading and genome stability.
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