Xu Xingzhi, Stern David F
Department of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06510, USA.
J Biol Chem. 2003 Mar 7;278(10):8795-803. doi: 10.1074/jbc.M211392200. Epub 2002 Dec 23.
NFBD1/KIAA0170 is a nuclear factor with an N-terminal FHA (forkhead-associated) domain and a tandem repeat of BRCT (breast cancer susceptibility gene-1 C terminus) domains, both of which are present in a number of proteins involved in DNA repair and/or DNA damage signaling pathways. We have investigated the association of NFBD1 with DNA damage responses. We found that the NFBD1 transcript is abundant in the testis relative to other tissues. NFBD1 is a chromatin-associated protein and is modified in G(2)/M phase or after DNA damage. NFBD1 phosphorylation in response to ionizing radiation (IR) was ATM-dependent. NFBD1 exhibited diffuse nuclear staining in the majority of untreated cells analyzed by indirect immunofluorescence and formed discrete nuclear foci after exposure to IR, UV radiation, and hydroxyurea treatment. IR induced NFBD1 foci within 1 min. The foci colocalized with gamma-H2AX foci, which have been previously shown to localize at sites of DNA double-strand breaks. IR-induced NFBD1 foci also colocalized with 53BP1 and MRE11/RAD50 foci. Taken together, these results suggest that NFBD1 is a mediator of DNA damage-dependent signaling.
NFBD1/KIAA0170是一种核因子，其具有N端FHA（叉头相关）结构域和BRCT（乳腺癌易感基因-1 C末端）结构域的串联重复序列，这两种结构域存在于许多参与DNA修复和/或DNA损伤信号通路的蛋白质中。我们研究了NFBD1与DNA损伤反应的关联。我们发现，相对于其他组织，NFBD1转录本在睾丸中丰富。NFBD1是一种与染色质相关的蛋白质，在G(2)/M期或DNA损伤后会发生修饰。电离辐射（IR）诱导的NFBD1磷酸化依赖于ATM。通过间接免疫荧光分析，在大多数未处理的细胞中，NFBD1呈现弥漫性核染色，而在暴露于IR、紫外线辐射和羟基脲处理后形成离散的核灶。IR在1分钟内诱导NFBD1灶形成。这些灶与γ-H2AX灶共定位，γ-H2AX灶先前已被证明定位于DNA双链断裂位点。IR诱导的NFBD1灶也与53BP1和MRE11/RAD50灶共定位。综上所述，这些结果表明NFBD1是DNA损伤依赖性信号传导的介质。
