Damaged beyond repair: alternative mechanisms to fix a chromosome break.

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Title Damaged beyond repair: alternative mechanisms to fix a chromosome break.
Publication Type thesis
School or College School of Biological Sciences
Department Biology
Author Bhandari, Jayaram
Date 2016
Description Chromosomes are constantly under threat from DNA damaging agents. The cellular response to DNA damage is important for cell survival and genome integrity. An accumulation of DNA damage could lead to cancer progression. Multiple pathways orchestrate the response to DNA damage, which primarily includes repair of the lesion, cell cycle regulation, and programmed cell death. The final outcome relies on the orchestration of these seemingly different pathways that ensures efficient and accurate response to DNA damage. In this thesis, we have addressed ways by which a cell can repair a broken end. We studied how a broken end generated by dicentric chromosome breakage in Drosophila could be repaired. We show that a broken end can invade the homologous chromosome to copy until the end of a chromosome to regenerate the ends, a mechanism termed as break-induced replication. Previous work demonstrated that a broken end generated in the male germline can be efficiently healed and transmitted to the next generation. Chk2 and p53 are critical DNA damage responders and promote cell survival and proliferation in the soma. Work presented here shows their roles in the germline following DNA damage. Chk2 helps in eliminating the cells with a broken chromosome whereas p53 is required to repopulate the germline following Chk2- mediated elimination.
Type Text
Publisher University of Utah
Subject BREAK-INDUCED-REPLICATION; CHK2; CHROMOSOME DAMAGE; GERMLINE; P53
Dissertation Name Master of Science
Language eng
Rights Management © Jayaram Bhandari
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s60046rc
Setname ir_etd
ID 1349752
Reference URL https://collections.lib.utah.edu/ark:/87278/s60046rc
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