東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Characterization of double-strand br...

Unal, Elcin.

FindBook

Google Book

Amazon

博客來

Characterization of double-strand break-induced cohesin domain assembly and function.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Characterization of double-strand break-induced cohesin domain assembly and function./
作者:	Unal, Elcin.
面頁冊數:	253 p.
附註:	Adviser: Douglas E. Koshland.
Contained By:	Dissertation Abstracts International68-11B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3288547
ISBN:	9780549313946

Characterization of double-strand break-induced cohesin domain assembly and function.
Unal, Elcin.

Characterization of double-strand break-induced cohesin domain assembly and function. - 253 p.

Adviser: Douglas E. Koshland.

Thesis (Ph.D.)--The Johns Hopkins University, 2008.

DNA dependent processes including transcription, replication, repair and chromosome segregation are all influenced by chromosome structure. Chromosome structure, in turn is shaped by the protein complexes that contain members of the Structural Maintenance of Chromosome (SMC) family. One of these protein complexes called cohesin has been implicated in accurate chromosome segregation and post-replicative repair of double-strand breaks (DSBs). Cohesin mediates sister chromatid cohesion by tethering sister chromatids from the time of their replication until their segregation in anaphase. It was thought that cohesin-mediated tethering established exclusively during S phase by Ctf7 is necessary and sufficient to ensure post-replicative DSB repair. In this study, we show that DSBs induce de novo recruitment of cohesins to the broken chromosomes and trigger activation of sister chromatid cohesion in post-replicative cells. Using budding yeast, we demonstrate that a single DSB induces the formation of a &sim;100 kb cohesin domain around the lesion. Our analyses suggest that the primary DNA damage checkpoint kinases, Mec1 or Tel1, phosphorylate histone H2AX to generate a large domain, which is permissive for cohesin binding. Cohesin binding to the phospho-H2AX domain is enabled by Mre11/Rad50/Xrs2 repair complex, as well as the components of the cohesin loading machinery. We further show DSBs induce genome-wide activation of sister chromatid cohesion in post-replicative cells by a Ctf7-dependent but replication-independent mechanism, challenging the prevalent view on cohesion establishment. Our studies reveal that Ctf7 has two functions; a cohesive activity and a conserved acetyltransferase activity, which triggers the generation of cohesion in response to the DSB and the DNA damage checkpoint. Finally, we provide evidence that the DSB induced cohesin is necessary for the efficiency as well as the specificity of post-replicative repair and that DSB-induced cohesion supports the fidelity of broken and to an extent unbroken chromosomes in response to DSBs. Altogether, our results implicate the direct involvement of cohesin complex in the maintenance of genomic integrity upon DNA damage and suggest that perturbations of DSB-specific cohesin pathway might play a role in tumorigenesis.

ISBN: 9780549313946Subjects--Topical Terms:

1017686
Biology, Cell.

Characterization of double-strand break-induced cohesin domain assembly and function.
LDR:03235nam 2200289 a 45 001 939095
005 20110512
008 110512s2008 ||||||||||||||||| ||eng d
020 $a 9780549313946
035 $a (UMI)AAI3288547
035 $a AAI3288547
040 $a UMI $c UMI
100 1 $a Unal, Elcin. $3 1263084
245 1 0 $a Characterization of double-strand break-induced cohesin domain assembly and function.
300 $a 253 p.
500 $a Adviser: Douglas E. Koshland.
500 $a Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7131.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2008.
520 $a DNA dependent processes including transcription, replication, repair and chromosome segregation are all influenced by chromosome structure. Chromosome structure, in turn is shaped by the protein complexes that contain members of the Structural Maintenance of Chromosome (SMC) family. One of these protein complexes called cohesin has been implicated in accurate chromosome segregation and post-replicative repair of double-strand breaks (DSBs). Cohesin mediates sister chromatid cohesion by tethering sister chromatids from the time of their replication until their segregation in anaphase. It was thought that cohesin-mediated tethering established exclusively during S phase by Ctf7 is necessary and sufficient to ensure post-replicative DSB repair. In this study, we show that DSBs induce de novo recruitment of cohesins to the broken chromosomes and trigger activation of sister chromatid cohesion in post-replicative cells. Using budding yeast, we demonstrate that a single DSB induces the formation of a &sim;100 kb cohesin domain around the lesion. Our analyses suggest that the primary DNA damage checkpoint kinases, Mec1 or Tel1, phosphorylate histone H2AX to generate a large domain, which is permissive for cohesin binding. Cohesin binding to the phospho-H2AX domain is enabled by Mre11/Rad50/Xrs2 repair complex, as well as the components of the cohesin loading machinery. We further show DSBs induce genome-wide activation of sister chromatid cohesion in post-replicative cells by a Ctf7-dependent but replication-independent mechanism, challenging the prevalent view on cohesion establishment. Our studies reveal that Ctf7 has two functions; a cohesive activity and a conserved acetyltransferase activity, which triggers the generation of cohesion in response to the DSB and the DNA damage checkpoint. Finally, we provide evidence that the DSB induced cohesin is necessary for the efficiency as well as the specificity of post-replicative repair and that DSB-induced cohesion supports the fidelity of broken and to an extent unbroken chromosomes in response to DSBs. Altogether, our results implicate the direct involvement of cohesin complex in the maintenance of genomic integrity upon DNA damage and suggest that perturbations of DSB-specific cohesin pathway might play a role in tumorigenesis.
590 $a School code: 0098.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Molecular. $3 1017719
690 $a 0307
690 $a 0369
690 $a 0379
710 2 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 68-11B.
790 $a 0098
790 1 0 $a Koshland, Douglas E., $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3288547