BRCT 结构域中的癌症易感性突变。

Cancer predisposing mutations in BRCT domains.

机构信息

Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.

出版信息

IUBMB Life. 2011 Jul;63(7):503-12. doi: 10.1002/iub.472.

DOI:10.1002/iub.472

PMID:21698754

Abstract

Members of the breast cancer 1 (BRCA1) carboxy-terminal (BRCT) superfamily are involved in the cellular response to the DNA damage sensing and repair, as well as in the cell cycle control. All proteins are characterized by one or more BRCT domain(s), which provides a flexible framework representing scaffolding element(s) in multi-protein complexes. In particular, BRCA1, nibrin (NBN), and microcephalin (MCPH1), generally considered as molecular models for cancer-prone syndromes, contain BRCT domains able to bind phosphorylated proteins. Mutations within the BRCT domains of BRCA1, NBN, and MCPH1 are responsible for cancer susceptibility, both at the homozygous and heterozygous status. Here, we report a critical analysis of: (i) the BRCT domain structure, (ii) the role of BRCA1, NBN, and MCPH1 in DNA damage sensing and repair as well as in cell cycle control, and (iii) the pathological effects of mutations within the BRCT domains of BRCA1, NBN, and MCPH1.

摘要

乳腺癌 1 号（BRCA1）羧基末端（BRCT）超家族的成员参与细胞对 DNA 损伤感应和修复的反应，以及细胞周期的控制。所有蛋白质的特征是一个或多个 BRCT 结构域，它提供了一个灵活的框架，代表多蛋白复合物中的支架元件。特别是，BRCA1、nibrin（NBN）和 microcephalin（MCPH1）通常被认为是癌症易感综合征的分子模型，它们含有能够结合磷酸化蛋白的 BRCT 结构域。BRCA1、NBN 和 MCPH1 的 BRCT 结构域内的突变导致癌症易感性，无论是纯合子还是杂合子状态。在这里，我们对以下内容进行了批判性分析：（i）BRCT 结构域结构，（ii）BRCA1、NBN 和 MCPH1 在 DNA 损伤感应和修复以及细胞周期控制中的作用，以及（iii）BRCA1、NBN 和 MCPH1 的 BRCT 结构域内突变的病理影响。