***** seminarMLから情報転載 *****

下記のように臨床研セミナーを開催します。Vaziri教授
は、動物細胞のDNA損傷チェックポイント、修復の研究
で大変著名です。今回分子生物学会に招聘され、来日
されますのでこの機会に最新の研究成果についてお話
いただきます。事前連絡なしにご自由にご参加くださ
い。なお臨床研は、上北沢に引っ越しました。最寄り
は京王線上北沢駅です。
http://www.rinshoken.or.jp/access/index.html
をご参照ください。お間違えのないように。


日時: 平成21年 12月 8日 (火曜日) 午前11:00 ~ 12:00

会場: (財)東京都医学研究機構 東京都臨床医学総合
研究所 2階会議室

演題:Integration of S-phase Checkpoint Signaling and Trans-Lesion
Synthesis (S期チェックポイントと損傷乗り越え修復によ
るゲノム制御)

演者 : Cyrus Vaziri教授 (University of North Carolina&s_comma; USA)



《要旨》

Cells are continuously exposed to intrinsic and extrinsic DNA-damaging
agents. Accurate replication and repair of damaged DNA is necessary
for maintenance of genome stability. Therefore&s_comma; cells have evolved
multiple mechanisms for integrating cell cycle progression with DNA
repair. DNA damage acquired during S-phase uncouples replicative
helicase and DNA polymerase activities on the leading strand&s_comma; thereby
generating tracts of ssDNA. Replication Protein A (RPA)-coated ssDNA
initiates an S-phase ‘checkpoint’ (mediated by ATR and Chk1 protein
kinases) that delays DNA synthesis and stabilizes stalled replication
forks. RPA-coated ssDNA also binds and recruits the ubiquitin E3
ligase Rad18 which promotes the engagement of specialized Trans-Lesion
Synthesis (TLS) DNA polymerases with stalled replication forks.
Because of flexible active sites that can accommodate the presence of
DNA lesions&s_comma; TLS polymerases allow maintenance of replication fork
progression when the genome is damaged. It is generally thought that
checkpoint signaling and TLS are initiated independently. However&s_comma; it
is likely that mechanisms exist to coordinate checkpoint signaling
with TLS. We have investigated the relationship between checkpoint
signaling and TLS. We show that TLS is necessary to allow appropriate
and timely attenuation of S-phase checkpoint signaling. Conversely&s_comma;
we show that checkpoint kinases influence the efficiency of TLS via
mechanisms involving phosphorylation of Rad18. Rad18 phosphorylation
likely represents an important mechanism for integrating checkpoint
signaling with TLS&s_comma; thereby ensuring appropriate recruitment of TLS
polymerases to replication forks. Integration of checkpoint signaling
and TLS likely minimizes acquisition of DNA damage-induced mutations
and contributes to maintenance of genomic stability.



〔世話人:ゲノム動態プロジェクト 正井 久雄〕
Hisao Masai
Genome Dynamics Project&s_comma;
Tokyo Metropolitan Institute of Medical Science&s_comma;
2-1-6 Kamikitazawa&s_comma; Setagaya-ku&s_comma; Tokyo 156-8506&s_comma; JAPAN
Tel: 81-3-5316-3231 Fax: 81-3-5316-3145; E-mail: masai-hs@igakuken.or.jp
http://www.rinshoken.or.jp/CB/index-jp.htm

正井 久雄
東京都臨床医学総合研究所 ゲノム動態プロジェクト
郵便番号 156-8506
所在地  東京都世田谷区上北沢二丁目1番6号
正井直通電話 03-5316-3231
研究室電話 03-5316-3117
研究室FAX 03-5316-3145
E-mail masai-hs@igakuken.or.jp



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