The Breast Cancer susceptibility protein 2 (BRCA2) is involved in mechanisms that maintain genome stability, including DNA repair, replication and cell division. These functions are ensured by the folded C-terminal DNA binding domain of BRCA2 but also by its large regions predicted to be disordered. Several studies have shown that disordered regions of BRCA2 are subjected to phosphorylation, thus regulating BRCA2 interactions through the cell cycle. The N-terminal region of BRCA2 contains two highly conserved clusters of phosphorylation sites between amino acids 75 and 210. Upon phosphorylation by CDK, the cluster 1 is known to become a docking site for the kinase PLK1. The cluster 2 is phosphorylated by PLK1 at least at two positions. Both of these phosphorylation clusters are important for mitosis progression, in particular for chromosome segregation and cytokinesis. In order to identify the phosphorylated residues and to characterize the phosphorylation sites preferences and their functional consequences within BRCA2 N-terminus, we have produced and analyzed the BRCA2 fragment from amino acid 48 to amino acid 284 (BRCA2_48–284). Here, we report the assignment of ¹H, ¹⁵N, ¹³CO, ¹³Cα and ¹³Cβ NMR chemical shifts of this region. Analysis of these chemical shifts confirmed that BRCA2_48–284 shows no stable fold: it is intrinsically disordered, with only short, transient α-helices.

中文翻译：

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人BRCA2 N端区域的1 H，13 C和15 N骨架共振分配

乳腺癌敏感性蛋白2（BRCA2）参与维持基因组稳定性的机制，包括DNA修复，复制和细胞分裂。通过折叠的BRCA2的C端DNA结合结构域以及通过预测其无序的大区域来确保这些功能。几项研究表明，BRCA2的无序区域会发生磷酸化，从而在整个细胞周期中调节BRCA2的相互作用。BRCA2的N端区域在氨基酸75和210之间包含两个高度保守的磷酸化位点簇。通过CDK进行磷酸化后，已知簇1成为激酶PLK1的停靠位点。团簇2至少在两个位置被PLK1磷酸化。这两个磷酸化簇对有丝分裂的进展都很重要，特别是对于染色体分离和胞质分裂。为了鉴定磷酸化残基并表征BRCA2 N末端内的磷酸化位点偏好及其功能后果，我们生产并分析了从氨基酸48到氨基酸284（BRCA2_48–284）。这里，我们报告的分配¹ H，¹⁵ N，¹³ CO，¹³ Cα和^13角CβNMR该区域的化学位移。对这些化学位移的分析证实，BRCA2 _48–284没有显示出稳定的折叠：它本质上是无序的，只有短而短暂的α螺旋。