- Title Information
- Title
- Ecdysone-Regulated DNA Amplification in Sciara coprophila
- Type of Resource
- text
- Name:
Personal
- Name Part
- Kadota, Léo
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Gerbi, Susan
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Helfand, Stephen
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Department of Molecular Biology, Cell Biology and Biochemistry
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2017
- Physical Description
- Extent
- 6, 61 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Sc. M.)--Brown University, 2017
- Genre (aat)
- theses
- Abstract
- Abstract of ‘Ecdysone-Regulated DNA Amplification in Sciara coprophila’, by Léo Kadota, Sc.M., Brown University, May 2017.
The eukaryotic genome contains thousands of origins (ORIs) of DNA replication, which are sequences where DNA synthesis begins in S phase of the cell cycle. The initiation of DNA replication begins in G1 phase in a tightly regulated process that is coordinated with cell cycle progression. This ensures that an ORI fires no more than once per cell cycle in order to evenly duplicate the genome that is subsequently evenly divided to daughter cells during mitosis. De-regulation of DNA replication initiation can lead to DNA re-replication, where an origin fires more than once during S phase, producing more than the diploid copy number. Locus-specific re-replication, also called DNA amplification, can lead to genomic instability, a hallmark of certain human cancers. DNA amplification of tumorigenic genes has also been documented in the cells of breast cancer tumors. It is therefore of general biological and medical importance to understand the mechanisms leading to DNA amplification.
It is hard to study the initiating events of DNA amplification in cancer cells. However, DNA amplification occurs as part of normal development during 4th larval instar in the larval salivary gland chromosomes of the fungus gnat Sciara coprophila. In human diseases, DNA amplification is a rare event and is therefore difficult to study experimentally. Sciara is a model organism that provides a unique opportunity to elucidate the mechanisms of DNA amplification in vivo. In Sciara, DNA amplification occurs at eighteen amplicon loci distributed across its four chromosomes. There is accumulating evidence that the steroid hormone ecdysone, the master regulator of insect development, acts through the ecdysone receptor as the amplification trigger for DNA amplification. This thesis describes experiments in which ecdysone injection into pre-amplification stage Sciara larvae prematurely induced DNA amplification, as measured by quantitative PCR, at all DNA amplicon loci. These observations support the hypothesis that ecdysone and its receptor act as the amplification trigger in Sciara. This thesis also details ongoing experiments aimed at determining whether ecdysone induces the transcription of small non-coding RNAs complementary to the amplicon origin, which could recruit replisome machinery to the amplicon ORIs to promote DNA amplification.
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00886601")
- Topic
- DNA replication
- Subject
- Topic
- sciara coprophila
- Subject
- Topic
- DNA amplification
- Subject
- Topic
- DNA puffs
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01108165")
- Topic
- Sciara
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00901308")
- Topic
- Ecdysone
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20170616
- Identifier:
DOI
- 10.7301/Z0NG4P3X
- Access Condition:
rights statement
(href="http://rightsstatements.org/vocab/InC/1.0/")
- In Copyright
- Access Condition:
restriction on access
- Collection is open for research.