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S. cerevisiae Ada2 and Bre1 has a role in histone post-translational modifications. Deletion of these genes causes deficiency in acetylation (Ada2) or ubiquitination (Bre1) of histones. Further, mutants lacking these genes or homologous genes showed different phenotypes in human and S. cerevisiae while treated with DNA damaging agents 4-NQO and MMS. Bre1 deficient cells showed 4-NQO sensitivity in S. cerevisiae and resistance in human cells. Since it has been shown that S. pombe is more close to mammals in chromatin regulation we wanted to examine S. pombe response against MMS and 4-NQO. By homologous recombination, genes were deleted and mutants were treated with different concentration of both the genotoxins. In accordance with a previous study, Ada2Δ showed sensitivity to MMS while Brl1Δ & Brl2Δ grew as wild type. Surprisingly, unlike S. cerevisiae, S. pombe showed resistance to 4-NQO and has a phenotype similar to the one found in human cells.

Chez la levure Saccharomyces cerevisiae, l’acétylation de l’histone H3 sur la Lysine 56 (H3K56ac) a lieu sur toutes les histones H3 nouvellement synthétisées qui sont déposées derrière les fourches de réplication. L’acétylation de H3K56 joue un rôle primordial dans l’assemblage de l’ADN lors la réplication et la réparation. L’acétylation de H3K56 joue également un rôle important dans la stabilité génomique et la stabilisation des fourches de réplication bloquée. En effet, les cellules dépourvues de H3K56ac sont sensibles au méthane sulfonate de méthyle (MMS) et à d’autres agents génotoxiques qui causent du stress réplicatif. Notre projet visait à investiguer les liens entre la protéine du réplisome Ctf4 et l’acétyltransférase d’histone Rtt109. Dans un premier lieu, la délétion de CTF4 a partiellement contré la sensibilité des cellules rtt109Δ au MMS. Notre analyse génétique a aussi montré que Ctf4, Rtt109, et le complexe Rtt101-Mms1-Mms22 agissent dans la même voie de réponse face à un stress réplicative. Nos résultats montrent que les cellules ctf4Δ et rtt109Δ présentent des foyers intenses du complexe de liaison à l'ADN simple-brin RPA en réponse au stress réplicatif, suggérant la formation excessive de régions d'ADN simple-brin aux fourches de réplication bloquées, ce qui conduit à une hyper activation des points de contrôle des dommages à l'ADN. Ces mutants présentent des ponts anaphase et des foyers persistants des protéines de recombinaison homologues Rad51 et Rad52 en réponse aux génotoxines, suggérant ainsi que la structure anormale des réplisomes bloqués peut compromettre leur récupération. Nos résultats indiquent également que la délétion des gènes de la RH (RAD51, RAD52, RAD54, RAD55 et MUS81) avec ctf4Δ et rtt109Δ respectivement, engendre une sensibilité synergique au MMS, suggérant que les cellules qui sont déficientes en H3K56 acétylation utilisent la RH pour réparer les dommages causés suite à un stress réplicatif. En conclusion, nos résultats suggèrent que les cellules déficientes en H3K56ac présentent des défauts de RH en réponse aux dommages à l’ADN induits par le MMS durant la phase S. / In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) occurs on all newly synthesized histones H3 that are deposited behind DNA replication forks. H3K56ac plays critical role in chromatin assembly during DNA replication and repair. H3K56ac is also required for genome stability and stabilization of stalled replication fork. Cells lacking H3K56ac are sensitive to methyl methane sulfonate and other drugs that cause replicative stress. In this thesis, we investigated the links between the replisome protein Ctf4 and the H3K56 acetyltransferase Rtt109. Deletion of CTF4 partially rescued the sensitivity of rtt109Δ cells to methyl methane sulfonate. Genetic analyses also showed that Ctf4, Rtt109, and the Rtt101-Mms1-Mms22 complex act in the same pathway to response to replicative stress. ctf4Δ and rtt109Δ cells displayed intense foci of the single-stranded DNA binding complex RPA during replicative stress, suggesting formation of excess single-stranded DNA regions at stalled replication forks, leading to hyper activation of DNA damage checkpoints. These mutants accumulated anaphase bridges and persistent foci of the homologous recombination proteins Rad51 and Rad52 in response to genotoxins, suggesting that abnormal DNA structure formed at stalled replisome may compromise their recovery. Deletion of HR genes (RAD51, RAD52, RAD54, RAD55 and MUS81) together with ctf4Δ and rtt109Δ presents synergistic sensitivity to MMS, suggesting that H3K56ac deficient cells use HR to repair the damages caused by replicative stress. Overall our results demonstrate that H3K56ac deficient cells cannot recover MMS- induced damages because HR is compromised in these mutants.

無線寬頻網路（Mobile Internet Broadband Network）的出現對於無線通訊產業、傳播媒體產業與影音內容產業產生了相當程度的影響，而數位化的科技發展更帶來通訊、傳播及平面媒體產業融合的可能性，無線寬頻影音串流（Mobile Internet Video Streaming）是一架構在此無線通訊媒體匯流後的新產物，透過觀察和分析它的演進發展，可以說明和解釋網路新媒體匯流造成傳統影音產業價值鏈的改變。 吾人將以無線通訊之影音播放技術之演進與發展，以及相對最先發生變化之影音產業經營環境，產生之影響，做產業價值鏈分析研究，進而了解產業經營環境之改變，新的價值創造流程及技術平台的關聯性。並藉由日本NTT DOCOMO之經驗，及對其供應商之觀察，了解台灣產業發展之可能趨勢，及策略建議藍圖。 本研究採P.W. Bane、S.P. Bradley & D.J. Collis (1998)三人提出之寬頻產業五層模式作為分析工具。五層模式分為內容(content)、包裝(package)、傳輸網路(transmission)、操作(manipulation) 及終端設備(terminal)五層架構。主要目的為以整體網路頻寬及技術演進的觀點進行分析五層間價值消長之關係，及整體網路之價值之改變。 我們發現在新的技術導入既有影音市場，由於網路之雙向特性，會產生網路效應及網路外部性，這些地方將產生新的價值所在，而擁有網路外部性的影音操作平台可獲得較高的價值。完整而消費者導向的影音操作平台，將首先累積產業之價值所在，影音操作平台的擁有者將成為產業的領導者，最終將成為標準的制定者。 影音內容的價值獲得來自網路外部性是經由更多人與內容來源(內容提供者)互動，造成下一次消費或其他使用者的外部性以及生產外部性，這樣的外部性是由虛擬連結產生．價值聚集於內容包裝層。 無線寬頻影音操作平台是服務成功的關鍵，有效的整合價值鏈及應用是必須在產業發展前完成，而完整的影音操作平台包含：內容製作壓縮平台、串流平台、訊息平台、及手機之用戶播放平台。 我們發現，新的技術導入市場，需要事先將價值鏈重新定義，整合出可行之新的商業模式，再依據新的價值鏈，新的服務流程去整合新的操作平台，投入服務後，由於是消費者導向的服務設計，可以降低消費者對新科技及新服務的學習門檻及進入障礙，而獲得市場認同。 / “Unlimited boundary & Ubiquitous content” Because of the improving the bandwidth & compression technology of mobile Internet, there are a very extremely industrial convergency in communication, broadcasting, & video audio content industry. There are several new technology including streaming, MPEG, multi media message, 3G which push the whole world going to a new Ubiquitous environment & totally change the old value chain of video audio industry, but we still have no ideal where it should go & what will happen next. We will try to research the technical evolution of video broadcasting which really influence our movie, TV industry. It will change the customer behavior of watching TV, or going to the movie. We especially want to find out where is the new value in the mobile Internet multi media industry. We will use the 5 liars analysis model of broadband industry (P.W. Bane、S.P. Bradley & D.J. Collis (1998))as our basic methodology to find out how the three vertical industries became a new 5 horizontal industries, which are content, package, transmission, manipulation, & terminal. We also want to know how they work internally & externally. We find that the video audio manipulation platform will become the key solution for this value chain, because of its network externality & network effect. The content providers also very important to provide the quality of contents to service the end customers. How to consolidate a new valuable services process & user friendly interface is the big issue here for whom will invest a large of money to creat the new mobile internet portal & new audio vedio manipulation platform. They must think not only the user interface of handset, but also the mechanism of profit sharing between these different providers who never work together in the history.