자료유형  

 학위논문

Control Number  

0016934401

International Standard Book Number  

9798380268110

Dewey Decimal Classification Number  

610

Main Entry-Personal Name  

Wong, Ka Man.

Publication, Distribution, etc. (Imprint  

[S.l.] : Stanford University., 2021

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2021

Physical Description  

1 online resource(88 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

General Note  

Advisor: Morrison, Ashby;Dixon, Scott;Fraser, Hunter;Rechem, Capucine van.

Dissertation Note  

Thesis (Ph.D.)--Stanford University, 2021.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약The distribution of initial DNA damage acquisition, repair rate and distribution of mutation are strongly influenced by global and local chromatin structure of the genome. Specifically, heterochromatic regions of the genome tend to acquire more DNA damage, repair slower and accumulate more mutations. However, whether losing functions of a chromatin modifier could alter carcinogen susceptibility remains unknown. We generated a CRISPR knock out mutant of RB1 (RB1KO), a known tumor suppressor that regulates heterochromatin structure in the genome. Comparative analysis of the genome wide map of UV damage in RB1KO and wild type reveals both local and global changes of carcinogen susceptibility in RB1KO. For instance, closed domain, as well as pericentric and subtelomeric regions of the genome become more susceptible in RB1KO. More importantly, some cancer driver genes, such as telomerase reverse transcriptase(TERT), becomes more susceptible to UV. Overall, our study demonstrates for the first time that the disruption of a tumor suppressor can alter global carcinogen susceptibility, potentially influencing mutation distributions. We established that the maintenance of proper global genome architecture and regional chromatin structure can potentially regulate DNA damage acquisition upon carcinogen exposure.

Subject Added Entry-Topical Term  

DNA methylation.

Subject Added Entry-Topical Term  

CRISPR.

Subject Added Entry-Topical Term  

Tumorigenesis.

Subject Added Entry-Topical Term  

Telomerase.

Subject Added Entry-Topical Term  

Lung cancer.

Subject Added Entry-Topical Term  

Retinoblastoma.

Subject Added Entry-Topical Term  

Mutation.

Subject Added Entry-Topical Term  

DNA damage.

Subject Added Entry-Topical Term  

Binding sites.

Subject Added Entry-Topical Term  

Skin cancer.

Subject Added Entry-Topical Term  

Chromosomes.

Subject Added Entry-Topical Term  

Carcinogens.

Subject Added Entry-Topical Term  

Genomes.

Subject Added Entry-Topical Term  

Epigenetics.

Subject Added Entry-Topical Term  

Melanoma.

Subject Added Entry-Topical Term  

Yeast.

Subject Added Entry-Topical Term  

Tumors.

Subject Added Entry-Topical Term  

Genes.

Subject Added Entry-Topical Term  

Cell cycle.

Subject Added Entry-Topical Term  

Transcription factors.

Subject Added Entry-Topical Term  

Ultraviolet radiation.

Subject Added Entry-Topical Term  

Biochemistry.

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Cellular biology.

Subject Added Entry-Topical Term  

Genetics.

Subject Added Entry-Topical Term  

Oncology.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 85-03B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:642083