生物遺傳的基礎(chǔ)是DNA復(fù)制，如果這一復(fù)制機(jī)制不起作用,，其結(jié)果可能是細(xì)胞缺失或是獲得額外的遺傳物質(zhì),，這些是大多數(shù)出生缺陷和癌癥基因組不穩(wěn)定的特點(diǎn),。
北卡羅來納大學(xué)醫(yī)學(xué)院的科學(xué)家們已經(jīng)發(fā)現(xiàn)CDT1是DNA復(fù)制所必需的,，CDT1在細(xì)胞周期后期很重要,，CDT1在有絲分裂中起著重要的作用。這一發(fā)現(xiàn)為解釋癌癥具有不只是基因組不穩(wěn)定的特征提供了一個可能的原因,。
這項(xiàng)新的研究刊登在Nature Cell Biology雜志上，該研究首次明確證實(shí)這樣一個DNA復(fù)制蛋白的雙重作用,。
UNC學(xué)校藥理和生物化學(xué)和生物物理學(xué)研究助理教授Jean Cook博士說
細(xì)胞周期中的一系列事件導(dǎo)致細(xì)胞其生長,、復(fù)制和分裂成兩個子細(xì)胞。它由四個不同的階段組成：G1期、S（DNA合成）期,，有絲分裂和G2,。Cook的研究主要集中在G1期。
一旦研究人員知道CDT1在有絲分裂中發(fā)揮作用,，他們希望弄清楚其中關(guān)鍵的過程,。Cook說，CDT1異常的細(xì)胞像腫瘤細(xì)胞,，在復(fù)制和有絲分裂中會遇到問題,。目前一個臨床試驗(yàn)試圖提高CDT1在癌細(xì)胞中的數(shù)量，將腫瘤細(xì)胞推到一個已經(jīng)岌岌可危致命的位置,。（生物谷：Bioon.com）
doi:10.1038/ncb2489
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Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore–microtubule attachment
Dileep Varma,Srikripa Chandrasekaran,Lynsie J. R. Sundin,Karen T. Reidy,Xiaohu Wan,Dawn A. D. Chasse,Kathleen R. Nevis,Jennifer G. DeLuca,E. D. Salmon& Jeanette Gowen Cook
Cdt1, a protein critical for replication origin licensing in G1 phase, is degraded during S phase but re-accumulates in G2 phase. We now demonstrate that human Cdt1 has a separable essential mitotic function. Cdt1 localizes to kinetochores during mitosis through interaction with the Hec1 component of the Ndc80 complex. G2-specific depletion of Cdt1 arrests cells in late prometaphase owing to abnormally unstable kinetochore–microtubule (kMT) attachments and Mad1-dependent spindle-assembly-checkpoint activity. Cdt1 binds a unique loop extending from the rod domain of Hec1 that we show is also required for kMT attachment. Mutation of the loop domain prevents Cdt1 kinetochore localization and arrests cells in prometaphase. Super-resolution fluorescence microscopy indicates that Cdt1 binding to the Hec1 loop domain promotes a microtubule-dependent conformational change in the Ndc80 complex in vivo. These results support the conclusion that Cdt1 binding to Hec1 is essential for an extended Ndc80 configuration and stable kMT attachment.
