NBS1 prevents chromatid-type aberrations through ATM-dependent interactions with SMC1
NBS1 prevents chromatid-type aberrations through ATM-dependent interactions with SMC1
复制标题
DOI：
10.1667/rr1357.1
复制
发表时间：
2008-09-01
影响因子：
3.4
通讯作者：
Komatsu, K.
中科院分区：
文献类型：
--
作者：
Antoccia, A.;Sakamoto, S.;Komatsu, K.
奈梅亨断裂综合征与共济失调毛细血管扩张症有几个共同的细胞特征，包括染色体不稳定和异常的S和G（2）期检查点调节。我们在这里表明，照射后，NBS 1物理相互作用与BRCA 1和SMC 1，一个组成部分的cohesin复合物，和它们的相互作用是完全废除AT细胞。值得注意的是，BRCA 1是NBS 1与SMC 1相互作用所必需的，而相反的情况并非如此，因为BRCA 1能够在没有NBS 1/SMC 1相互作用的情况下与NBS 1结合，如在MRE 11-或RAD 50-缺陷细胞中所观察到的。这表明ATM和BRCA 1是NBS 1/SMC 1相互作用的上游。此外，NBS 1与SMC 1的相互作用需要NBS在N-末端和C-末端的保守结构域，因为它们分别是NBS 1与BRCA 1和MRE 11/ATM结合所必需的。NBS 1与SMC 1的相互作用以及由此产生的磷酸化在缺乏NBS 1的N-或C-末端的克隆中受到损害，因此，照射后染色单体型畸变增强。我们的研究结果表明，ATM在促进辐射诱导的NBS 1与SMC 1在BRCA 1的存在下的相互作用，导致染色体的完整性的维护中起着重要的作用。(c)2008年，辐射研究协会。
Nijmegen breakage syndrome shares several common cellular features with ataxia telangiectasia, including chromosomal instability and aberrant S- and G(2)-phase checkpoint regulation. We show here that after irradiation, NBS1 interacts physically with both BRCA1 and SMC1, a component of the cohesin complex, and that their interactions are completely abolished in AT cells. It is noted that BRCA1 is required for the interaction of NBS1 with SMC1, whereas the reverse is not the case, since BRCA1 is able to bind to NBS1 in the absence of an NBS1/SMC1 interaction as observed in MRE11- or RAD50-deficient cells. This indicates that ATM and BRCA1 are upstream of the NBS1/SMC1 interaction. Furthermore, the interaction of NBS1 with SMC1 requires both conserved domains of NBS in the N-terminus and the C-terminus, since they are indispensable for binding of NBS1 to BRCA1 and to MRE11/ATM, respectively. The interaction of NBS1 with SMC1 and the resulting phosphorylation are compromised in the clones lacking either the N- or C-terminus of NBS1, and as a consequence, chromatid-type aberrations are enhanced after irradiation. Our results reveal that ATM plays a fundamental role in promoting the radiation-induced interaction of NBS1 with SMC1 in the presence of BRCA1, leading to the maintenance of chromosomal integrity. (c) 2008 by Radiation Research Society.