CHU de Québec Research Center, Oncology Division, 9 McMahon, Québec City, QC, G1R 3S3, Canada; CHU de Québec Research Center, Endocrinology and Nephrology Division, 2705 Bld Laurier, Québec City, QC, G1V 4G2, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Québec City, QC, G1V 0A6, Canada.
CHU de Québec Research Center, Oncology Division, 9 McMahon, Québec City, QC, G1R 3S3, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Québec City, QC, G1V 0A6, Canada.
Trends Biochem Sci. 2019 Mar;44(3):226-240. doi: 10.1016/j.tibs.2018.10.008. Epub 2019 Jan 10.
Partner and Localizer of BRCA2 (PALB2) has emerged as an important and versatile player in genome integrity maintenance. Biallelic mutations in PALB2 cause Fanconi anemia (FA) subtype FA-N, whereas monoallelic mutations predispose to breast, and pancreatic familial cancers. Herein, we review recent developments in our understanding of the mechanisms of regulation of the tumor suppressor PALB2 and its functional domains. Regulation of PALB2 functions in DNA damage response and repair occurs on multiple levels, including homodimerization, phosphorylation, and ubiquitylation. With a molecular emphasis, we present PALB2-associated cancer mutations and their detailed analysis by functional assays.
BRCA2（PALB2）的伴侣和定位子已成为维持基因组完整性的重要和多功能的参与者。PALB2 的双等位基因突变导致范可尼贫血（FA）亚型 FA-N，而单等位基因突变易患乳腺癌和胰腺家族性癌症。本文综述了我们对肿瘤抑制因子 PALB2 及其功能结构域的调控机制的最新认识。PALB2 在 DNA 损伤反应和修复中的功能调节发生在多个水平，包括同源二聚化、磷酸化和泛素化。本文以分子为重点，介绍了 PALB2 相关的癌症突变及其通过功能测定的详细分析。
