Abstract

While the assembly of proteins that replicate DNA has been investigated in detail, relatively little is known about the way in which the strands of DNA are looped at the fork. Over 15 years ago, a model was proposed in which the lagging strand loops back at the fork and engages a second molecule of DNA polymerase This dimeric polymerase assembly and DNA loop was envisioned to couple leading and lagging strand replication with the proteins involved in lagging strand synthesis being recycled from the end of a completed Okazaki fragment to the next primer. Unfortunately, little direct evidence for looping exists. In the ongoing work of this laboratory, electron microscopy(EM) has been used to examine products of in vitro replication reactions. Loops of DNA at the replication fork were visualized. Understanding looping and how loops grow and reform with Okazaki fragment synthesis is the goal of this project.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031819-15
Application #
2734468
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1983-04-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
15
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Nicholls, Thomas J; Nadalutti, Cristina A; Motori, Elisa et al. (2018) Topoisomerase 3? Is Required for Decatenation and Segregation of Human mtDNA. Mol Cell 69:9-23.e6
Kar, Anirban; Jones, Nathan; Arat, N Özlem et al. (2018) Long repeating (TTAGGG) n single-stranded DNA self-condenses into compact beaded filaments stabilized by G-quadruplex formation. J Biol Chem 293:9473-9485
Amunugama, Ravindra; Willcox, Smaranda; Wu, R Alex et al. (2018) Replication Fork Reversal during DNA Interstrand Crosslink Repair Requires CMG Unloading. Cell Rep 23:3419-3428
Zhu, Cheng; Beck, Matthew V; Griffith, Jack D et al. (2018) Large SOD1 aggregates, unlike trimeric SOD1, do not impact cell viability in a model of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 115:4661-4665
Erdel, Fabian; Kratz, Katja; Willcox, Smaranda et al. (2017) Telomere Recognition and Assembly Mechanism of Mammalian Shelterin. Cell Rep 18:41-53
Bermek, Oya; Weller, Sandra K; Griffith, Jack D (2017) The UL8 subunit of the helicase-primase complex of herpes simplex virus promotes DNA annealing and has a high affinity for replication forks. J Biol Chem 292:15611-15621
Prasad, Rajendra; Ça?layan, Melike; Dai, Da-Peng et al. (2017) DNA polymerase ?: A missing link of the base excision repair machinery in mammalian mitochondria. DNA Repair (Amst) 60:77-88
Sepsiova, Regina; Necasova, Ivona; Willcox, Smaranda et al. (2016) Evolution of Telomeres in Schizosaccharomyces pombe and Its Possible Relationship to the Diversification of Telomere Binding Proteins. PLoS One 11:e0154225
Kar, Anirban; Willcox, Smaranda; Griffith, Jack D (2016) Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops. Nucleic Acids Res 44:9369-9380
Holmes, J Bradley; Akman, Gokhan; Wood, Stuart R et al. (2015) Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication. Proc Natl Acad Sci U S A 112:9334-9

Showing the most recent 10 out of 183 publications