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DNA helicases and associated factors in genome stability

DNA 解旋酶和基因组稳定性的相关因素

基本信息

批准号：
10810234
负责人：
Matthew Linne Bochman
金额：
$ 0.84万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10810234
关键词：
Alleles Binding Biological Assay Biological Models Biological Sciences Biomedical Research Chemistry Clinic Complement Custom DNA Interstrand Cross-Link Repair DNA Maintenance DNA Repair DNA biosynthesis Data Development Disease Family Functional disorder Funding G-Quartets Genes Genetic Genetic Recombination Genome Genome Stability Goals Group Meetings Helicase Gene Human In Vitro Indiana Knowledge Link Maintenance Mass Spectrum Analysis Molecular Molecular Biology Mutate Mutation Patients Productivity Research Research Project Grants Role Saccharomyces cerevisiae Structure Techniques Telomere Maintenance Testing Toxic effect Universities Work career cell type crosslink experience genome integrity helicase in vivo insight member model organism mutant nanobodies next generation sequencing overexpression posters repaired summer research symposium therapeutic target undergraduate research undergraduate research experience virtual yeast genetics

项目摘要

PROJECT SUMMARY DNA helicases function in virtually all aspects of DNA replication, recombination, and repair. As such, they are vital to maintaining genome integrity and are disease linked when mutated. Despite many in vivo and in vitro advances in working with helicases, there is a gap in knowledge connecting mutant alleles of helicase genes to the treatment of patients in clinics. The objective of my research is to gain mechanistic insight into how DNA helicases function in genome maintenance and why their dysfunction leads to disease. Toward this goal, we are studying PIF1 and RecQ family helicases, which are evolutionarily conserved and because mutations in the human genes encoding these helicases are associated with multiple diseases. Our current work focuses on the roles of RecQ helicases in DNA inter-strand crosslink (ICL) repair and RecQ and Pif1 helicases in telomere maintenance. To perform this work, we will employ a variety of classic and cutting edge experimental techniques, from standard in vitro enzymatic assays and model organism genetics to next- generation sequencing, crosslinking mass spectrometry, and the development of custom click chemistry probes. Overall, this work will provide fundamental data critical to understanding how PIF1 and RecQ family helicases aid in the maintenance of genome stability, and it will ultimately lead to therapeutic targets and treatments for helicase-linked diseases. In this application, I am requesting funds to support a 10-week research experience for Ms. Morgan Roush in my lab during the summer of 2023. The purpose of this project is to enable Ms. Roush to gain research experience in molecular biology and yeast genetics to support her goals to pursue a career in biomedical research. Ms. Roush’s research project will examine the link between G-quadruplex (G4) DNA stability and genome integrity. Ms. Roush aims to generate Saccharomyces cerevisiae strains lacking the enzymatic activity of one or more DNA helicases implicated in G4 structure unwinding and maintenance. She will then test the effects of over-expressing a G4-binding and -stabilizing nanobody in these strains to compare the toxicity of G4 stabilization to wild-type cells containing a full complement of helicases. Ms. Roush will attend and present at our weekly group meeting, and she will present a poster in the Indiana University Undergraduate Research Symposium at the end of summer 2023. It is my further hope that her summer research experience is positive and that she will remain a productive member of my lab until she graduates.

项目总结

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fanconi anemia-independent DNA inter-strand crosslink repair in eukaryotes.

DOI：
10.1016/j.pbiomolbio.2020.08.005
发表时间：
2020-12
期刊：
Progress in biophysics and molecular biology
影响因子：
3.8
作者：
Rogers CM;Simmons Iii RH;Fluhler Thornburg GE;Buehler NJ;Bochman ML
通讯作者：
Bochman ML

Pif1 Activity is Modulated by DNA Sequence and Structure.

DOI：
10.1021/acs.biochem.1c00614
发表时间：
2022-01-04
期刊：
Biochemistry
影响因子：
2.9
作者：
Nickens DG;Bochman ML
通讯作者：
Bochman ML

Characterization of the telomerase modulating activities of yeast DNA helicases.

DOI：
10.1016/bs.mie.2021.08.005
发表时间：
2021
期刊：
Methods in enzymology
影响因子：
0
作者：
Nickens DG;Bochman ML
通讯作者：
Bochman ML

Overcoming stochastic variations in culture variables to quantify and compare growth curve data.

DOI：
10.1002/bies.202100108
发表时间：
2021-08
期刊：
BioEssays : news and reviews in molecular, cellular and developmental biology
影响因子：
0
作者：
Sausen CW;Bochman ML
通讯作者：
Bochman ML

Lysine acetylation regulates the activity of nuclear Pif1