The bloom syndrome helicase is a substrate of the mitotic cdc2 kinase
The bloom syndrome helicase is a substrate of the mitotic cdc2 kinase
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DOI：
10.4161/cc.5.15.3122
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发表时间：
2006-08-01
期刊：
影响因子：
4.3
通讯作者：
Amor-Gueret, Mounira
中科院分区：
文献类型：
--
作者：
Bayart, Emilie;Dutertre, Stephanie;Amor-Gueret, Mounira
Bloom综合征(BS)是一种罕见的人类常染色体隐性遗传病，其特征是显著的遗传不稳定，与影响普通人群的多种癌症的易感性大大增加有关。BS是通过BLM基因的两个拷贝的突变而产生的，该基因编码一个被鉴定为RecQ家族成员的3‘-5’DNA解旋酶。几项研究支持BLM在细胞对DNA损伤和复制分叉停滞的反应中发挥重要作用。然而，博鳌亚洲论坛的具体职能(S)仍不清楚(S)。BLM蛋白在有丝分裂过程中强烈表达和磷酸化，但关于这种磷酸化的起源和意义的信息很少。我们在这里表明，ATM激酶在BLM有丝分裂磷酸化过程中的作用有限。我们还证明了BLM在体外被有丝分裂的cdc2激酶在多个位置直接磷酸化，并鉴定了有丝分裂BLM的两个新的磷酸化位点：Ser-714和Thr-766。我们的结果确定BLM解旋酶是cdc2的新底物，这可能对BLM在有丝分裂中的作用具有潜在的生理学意义。
Bloom syndrome (BS) is a rare human autosomal recessive disorder characterized by marked genetic instability associated with greatly increased predisposition to a wide range of cancers affecting the general population. BS arises through mutations in both copies of the BLM gene which encodes a 3'-5' DNA helicase identified as a member of the RecQ family. Several studies support a major role for BLM in the cellular response to DNA damage and stalled replication forks. However, the specific function(s) of BLM remain( s) unclear. The BLM protein is strongly expressed and phosphorylated during mitosis, but very little information is available about the origin and the significance of this phosphorylation. We show here that ATM kinase provides only a limited contribution to the mitotic phosphorylation of BLM. We also demonstrate that BLM is directly phosphorylated at multiple sites in vitro by the mitotic cdc2 kinase, and identify two new sites of mitotic BLM phosphorylation: Ser-714 and Thr-766. Our results identify BLM helicase as a new substrate for cdc2, which may have potential physiological implications for the role of BLM in mitosis.