Structural basis for recruitment of BRCA2 by PALB2
Structural basis for recruitment of BRCA2 by PALB2
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DOI：
10.1038/embor.2009.126
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发表时间：
2009-09-01
期刊：
影响因子：
7.7
通讯作者：
Pearl, Laurence H.
中科院分区：
文献类型：
--
作者：
Oliver, Antony W.;Swift, Sally;Pearl, Laurence H.
乳腺癌2，早发蛋白（BRCA 2）是通过同源重组修复DNA损伤的核心。BRCA 2将重组酶RAD 51募集到损伤位点，调节其组装成核蛋白丝，从而促进同源重组。BRCA 2定位于核灶需要其与BRCA 2的伴侣和定位子（PALB 2）相关，其中突变与癌症易感性以及范可尼贫血的N亚型相关。我们已经确定了与BRCA 2肽复合的PALB 2羧基末端β-螺旋桨结构域的结构。该结构显示了这种重要蛋白质相互作用的分子决定因素，并解释了PALB 2中癌症相关截短突变体和BRCA 2氨基末端区域错义突变的影响。
The breast cancer 2, early onset protein (BRCA2) is central to the repair of DNA damage by homologous recombination. BRCA2 recruits the recombinase RAD51 to sites of damage, regulates its assembly into nucleoprotein filaments and thereby promotes homologous recombination. Localization of BRCA2 to nuclear foci requires its association with the partner and localizer of BRCA2 (PALB2), mutations in which are associated with cancer predisposition, as well as subtype N of Fanconi anaemia. We have determined the structure of the PALB2 carboxy terminal beta-propeller domain in complex with a BRCA2 peptide. The structure shows the molecular determinants of this important protein protein interaction and explains the effects of both cancer associated truncating mutants in PALB2 and missense mutations in the amino terminal region of BRCA2.