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Quantitative analysis of DNA repair ...

Verkhedkar, Ketki Dinesh.

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Quantitative analysis of DNA repair and p53 in individual human cells.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Quantitative analysis of DNA repair and p53 in individual human cells./
Author:	Verkhedkar, Ketki Dinesh.
Description:	124 p.
Notes:	Source: Dissertation Abstracts International, Volume: 74-06(E), Section: B.
Contained By:	Dissertation Abstracts International74-06B(E).
Subject:	Biology, Systematic. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3553498
ISBN:	9781267929792

Quantitative analysis of DNA repair and p53 in individual human cells.
Verkhedkar, Ketki Dinesh.

Quantitative analysis of DNA repair and p53 in individual human cells. - 124 p.

Source: Dissertation Abstracts International, Volume: 74-06(E), Section: B.

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

The goal of my research was to obtain a quantitative understanding of the mechanisms of DNA double-strand break (DSB) repair, and the activation of the tumor suppressor p53 in response to DSBs in human cells.

ISBN: 9781267929792Subjects--Topical Terms:

1676856
Biology, Systematic.

Quantitative analysis of DNA repair and p53 in individual human cells.
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020 $a 9781267929792
035 $a (MiAaPQ)AAI3553498
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100 1 $a Verkhedkar, Ketki Dinesh. $3 2102183
245 1 0 $a Quantitative analysis of DNA repair and p53 in individual human cells.
300 $a 124 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-06(E), Section: B.
500 $a Adviser: Galit Lahav.
502 $a Thesis (Ph.D.)--Harvard University, 2012.
520 $a The goal of my research was to obtain a quantitative understanding of the mechanisms of DNA double-strand break (DSB) repair, and the activation of the tumor suppressor p53 in response to DSBs in human cells.
520 $a In Chapter 2, we investigated how the kinetics of repair, and the balance between the alternate DSB repair pathways, nonhomologous end-joining (NHEJ) and homologous recombination (HR), change with cell cycle progression. We developed fluorescent reporters to quantify DSBs, HR and cell cycle phase in individual, living cells. We show that the rates of DSB repair depend on the cell cycle stage at the time of damage. We find that NHEJ is the dominant repair mechanism in G1 and in G2 cells even in the presence of a functional HR pathway. S and G2 cells use both NHEJ and HR, and higher use of HR strongly correlates with slower repair. Further, we demonstrate that the balance between NHEJ and HR changes gradually with cell cycle progression, with a maximal use of HR at the peak of active replication in mid-S. Our results establish that the presence of a sister chromatid does not affect the use of HR in human cells.
520 $a Chapter 3 examines the sensitivity of the p53 pathway to DNA DSBs. We combined our fluorescent reporter for DSBs with a fluorescent reporter for p53, to quantify the level of damage and p53 activation in single cells. We find that the probability of inducing a p53 pulse increases linearly with the amount of damage. However, cancer cells do not have a distinct threshold of DSBs above which they uniformly induce p53 accumulation. We demonstrate that the decision to activate p53 is potentially controlled by cell-specific factors. Finally, we establish that the rates of DSB repair do not affect the decision to activate p53 or the dynamical properties of the p53 pulse.
520 $a Collectively, this work emphasizes the importance of collecting quantitative dynamic information in single cells in order to gain a comprehensive understanding of how different DNA damage response pathways function in a coordinated manner to maintain genomic integrity.
590 $a School code: 0084.
650 4 $a Biology, Systematic. $3 1676856
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Genetics. $3 1017730
690 $a 0423
690 $a 0307
690 $a 0379
690 $a 0369
710 2 $a Harvard University. $b Systems Biology. $3 2096528
773 0 $t Dissertation Abstracts International $g 74-06B(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=3553498