東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Genome-Wide Loss-of-Function Genetic...

Burrows, Anna Elizabeth.

Linked to FindBook

Google Book

Amazon

博客來

Genome-Wide Loss-of-Function Genetic Screens Identify Novel Senescence Genes and Putative Tumor Suppressors.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Genome-Wide Loss-of-Function Genetic Screens Identify Novel Senescence Genes and Putative Tumor Suppressors./
Author:	Burrows, Anna Elizabeth.
Description:	211 p.
Notes:	Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.
Contained By:	Dissertation Abstracts International73-11B(E).
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3513906
ISBN:	9781267445377

Genome-Wide Loss-of-Function Genetic Screens Identify Novel Senescence Genes and Putative Tumor Suppressors.
Burrows, Anna Elizabeth.

Genome-Wide Loss-of-Function Genetic Screens Identify Novel Senescence Genes and Putative Tumor Suppressors. - 211 p.

Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.

Thesis (Ph.D.)--Harvard University, 2012.

During every cell cycle and upon exogenous stress, tumor suppression programs are engaged to ensure genomic stability. In response to replicative aging and oncogenic stimuli, the p53 and Rb pathways are activated to prevent the proliferation of damaged cells. Several lines of evidence suggest that escape from senescence is a crucial early step in oncogenic progression. A major challenge in the cancer field is to combine genomic information regarding cancer-associated genetic changes with high-throughput functional studies, in order to confirm genetic requirements and pinpoint biological roles of these perturbed genes in oncogenesis. Furthermore, a complete genetic understanding of replicative senescence, and how it might be bypassed, is lacking. We describe here two genome scale loss-of-function genetic screens that interrogate these tumor suppressor programs. We utilized a unique sensitization approach to isolate senescence pathways and unmask compensatory mechanisms that may have been difficult to identify in previous studies. These genetic screens have generated comprehensive and validated datasets of putative senescence and p53 pathway genes. We present this dataset as a high-quality resource for further investigation into these biological pathways.

ISBN: 9781267445377Subjects--Topical Terms:

1017686
Biology, Cell.

Genome-Wide Loss-of-Function Genetic Screens Identify Novel Senescence Genes and Putative Tumor Suppressors.
LDR:03341nam a2200289 4500 001 1961788
005 20140722092940.5
008 150210s2012 ||||||||||||||||| ||eng d
020 $a 9781267445377
035 $a (MiAaPQ)AAI3513906
035 $a AAI3513906
040 $a MiAaPQ $c MiAaPQ
100 1 $a Burrows, Anna Elizabeth. $3 2097737
245 1 0 $a Genome-Wide Loss-of-Function Genetic Screens Identify Novel Senescence Genes and Putative Tumor Suppressors.
300 $a 211 p.
500 $a Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.
500 $a Adviser: Stephen J. Elledge.
502 $a Thesis (Ph.D.)--Harvard University, 2012.
520 $a During every cell cycle and upon exogenous stress, tumor suppression programs are engaged to ensure genomic stability. In response to replicative aging and oncogenic stimuli, the p53 and Rb pathways are activated to prevent the proliferation of damaged cells. Several lines of evidence suggest that escape from senescence is a crucial early step in oncogenic progression. A major challenge in the cancer field is to combine genomic information regarding cancer-associated genetic changes with high-throughput functional studies, in order to confirm genetic requirements and pinpoint biological roles of these perturbed genes in oncogenesis. Furthermore, a complete genetic understanding of replicative senescence, and how it might be bypassed, is lacking. We describe here two genome scale loss-of-function genetic screens that interrogate these tumor suppressor programs. We utilized a unique sensitization approach to isolate senescence pathways and unmask compensatory mechanisms that may have been difficult to identify in previous studies. These genetic screens have generated comprehensive and validated datasets of putative senescence and p53 pathway genes. We present this dataset as a high-quality resource for further investigation into these biological pathways.
520 $a We have uncovered several genes in distinct biological pathways which have not been demonstrated to have a functional role in senescence, and which may be putative tumor suppressors. We have identified BRD7 and BAF180, two SWI/SNF components, as critical regulators of p53. BRD7 and BAF180 are required for p53 activity and p21 expression during replicative and oncogene-induced senescence, and evidence suggests that they are inactivated in human cancer. In addition, we have uncovered a role for the deubiquitinating enzyme USP28 in the regulation of p53 accumulation during senescence, such that loss of USP28 results in bypass of the senescence program. We have also investigated several other novel senescence genes including SEMA6A, SEMA3b, and TMEM154. We have found that the expression of these genes is highly regulated during senescence by distinct means, including both p53-dependent and p53-independent mechanisms. These results demonstrate the efficacy of our sensitized screening approach, and also highlight the emerging view that the senescence program requires the combined action of multiple biological pathways for its execution.
590 $a School code: 0084.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Genetics. $3 1017730
690 $a 0379
690 $a 0369
710 2 $a Harvard University. $b Biology: Medical Sciences, Division of. $3 2097738
773 0 $t Dissertation Abstracts International $g 73-11B(E).
790 $a 0084
791 $a Ph.D.
792 $a 2012
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3513906