The long-term objective of this work is to understand the mechanisms that organisms use to ensure that genome integrity is maintained from generation to generation and from cell to cell. Genomes are subject to damage in a variety of forms and have evolved a variety of mechanisms to repair damage, or to cope with failure. To maintain chromosome stability, the linear chromosomes of eukaryotes must be capped with telomeres. Loss of a single telomere is a particularly challenging form of genome damage, and most often results in apoptosis, rather than successful repair. Two forms of repair are known for this type of damage: healing, which refers to the addition of a new telomere on the non-telomeric end of a chromosome; or Break-Induced Replication (BIR), in which the broken chromosome copies information from another chromosome to replace the end that it is missing. Both types of repair are associated with alterations in the genome. Since this is generally undesirable, these modes of repair may be considered repair of last resort. The work proposed here will investigate the germline responses to telomere loss. The goals are to identify the genetic controls that are used to detect and eliminate cells with this form of damage. Differences in the responses between male and female germlines will be explored. The experiments proposed here will also investigate the BIR mode of repair, which has not been previously demonstrated in any germline. This type of repair has additional interest because of its similarity to a form of telomere maintenance found in some cancer cells.

Public Health Relevance

When damaged chromosomes are passed from parent to offspring, they may cause developmental disorders. When chromosome damage occurs during development, it may lead to cancer. This work investigates the mechanisms that are used to prevent the transmission of damaged chromosomes.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Molecular Genetics A Study Section (MGA)
Program Officer
Willis, Kristine Amalee
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Utah
Schools of Arts and Sciences
Salt Lake City
United States
Zip Code
Karg, Travis J; Golic, Kent G (2018) Photoconversion of DAPI and Hoechst dyes to green and red-emitting forms after exposure to UV excitation. Chromosoma 127:235-245
Kurzhals, Rebeccah L; Fanti, Laura; Ebsen, A C Gonzalez et al. (2017) Chromosome Healing Is Promoted by the Telomere Cap Component Hiphop in Drosophila. Genetics 207:949-959
Rong, Yikang S; Golic, Mary M; Golic, Kent G (2016) The pugilistDominant Mutation of Drosophila melanogaster: A Simple-Sequence Repeat Disorder Reveals Localized Transport in the Eye. PLoS One 11:e0151377
Chakraborty, Riddhita; Li, Ying; Zhou, Lei et al. (2015) Corp Regulates P53 in Drosophila melanogaster via a Negative Feedback Loop. PLoS Genet 11:e1005400
Akbari, Omar S; Bellen, Hugo J; Bier, Ethan et al. (2015) BIOSAFETY. Safeguarding gene drive experiments in the laboratory. Science 349:927-9
Hill, Hunter; Golic, Kent G (2015) Preferential Breakpoints in the Recovery of Broken Dicentric Chromosomes in Drosophila melanogaster. Genetics 201:563-72
Titen, Simon W A; Lin, Ho-Chen; Bhandari, Jayaram et al. (2014) Chk2 and p53 regulate the transmission of healed chromosomes in the Drosophila male germline. PLoS Genet 10:e1004130
Golic, Kent G (2013) RNA-guided nucleases: a new era for engineering the genomes of model and nonmodel organisms. Genetics 195:303-8
Kurzhals, Rebeccah L; Titen, Simon W A; Xie, Heng B et al. (2011) Chk2 and p53 are haploinsufficient with dependent and independent functions to eliminate cells after telomere loss. PLoS Genet 7:e1002103
Golic, Mary M; Golic, Kent G (2011) A simple and rapid method for constructing ring-X chromosomes in Drosophila melanogaster. Chromosoma 120:159-64

Showing the most recent 10 out of 19 publications