Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2
Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2
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DOI：
10.1016/j.molcel.2006.05.022
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发表时间：
2006-06-23
期刊：
影响因子：
16
通讯作者：
Livingston, David M.
中科院分区：
文献类型：
--
作者：
Xia, Bing;Sheng, Qing;Livingston, David M.
BRCA 2突变使携带者易患乳腺癌和卵巢癌，也可导致其他癌症和范可尼贫血。BRCA 2通过实现基于同源重组（HR）的无错误DNA双链断裂修复（DSBR）和S期内DNA损伤检查点控制来充当基因组完整性的“看护者”。这里描述的是PALB 2的鉴定，PALB 2是BRCA 2结合蛋白。PALB 2与BRCA 2共定位于核灶中，促进其在关键核结构中的定位和稳定性（例如，染色质和核基质），并使其重组修复和检查点功能。此外，在乳腺癌患者中鉴定的但迄今未知生物学/临床后果的多个生殖系BRCA 2错义突变似乎破坏PALB 2结合并使BRCA 2 HR/DSBR功能丧失。因此，PALB 2许可BRCA 2的关键细胞生化特性，并确保其肿瘤抑制功能。
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.