Biosciences Graduate Program

Marc S. Wold, PhD

Portrait

Professor of Biochemistry
Professor of Radiation Oncology

Contact Information

Primary Office: 3107 MERF
Iowa City, IA 52242
Primary Office Phone: 319-335-6784

Email: marc-wold@uiowa.edu
Web: Wold Laboratory

Education


BS, Chemistry, California Institute of Technology
PhD, Biochemistry, The Johns Hopkins University

Post Doctoral, Molecular Biology & Genetics, The Johns Hopkins University

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Biochemistry PhD
Free Radical and Radiation Biology Graduate Program
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program

Research Summary

The human genome is composed of ~4x109 base pairs of DNA. In order to grow, a human cell must precisely duplicate this entire genome each cell cycle and continuously protect it from damage or modification. Defects in DNA replication or repair result in higher rates of mutation, chromosome instability and have a direct role in a number of human diseases such as contributing to the development of cancer or causing genetic diseases such as Fragile X and Xeroderma Pigmentosum. Replication protein A (RPA) is a multi-functional, single-stranded DNA-binding protein. RPA is essential for DNA replication, DNA repair, recombination and coordination of the cellular response to DNA damage. RPA is composed of six structurally conserved DNA binding domains that are distributed in three subunits. The functions of these domains are poorly understood. RPA is also phosphorylated during S-phase and in response to DNA damage. Recent studies have shown that RPA hyper-phosphorylation modulates RPA activity and plays a role in the cellular response to DNA damage; however, the mechanism of this regulation is also poorly understood. Our current research focuses on utilizing a combination of in vitro and in vivo approaches to define functions of the domains of RPA and understanding the role of RPA in regulating cellular DNA metabolism. We are using molecular approaches to generate specific mutant forms of RPA. Biochemical and structural analyses are used to define the interactions of RPA with the different DNA substrates and protein complexes. We have also have recently established a system that uses RNAi and plasmid directed expression of exogenous genes to examine the activity of wild-type and mutant RPA genes in human cells. These studies will lead to a better understanding of the molecular mechanisms of cellular DNA metabolism and will contribute to developing new treatments for diseases associated with defects in DNA repair or replication.

Center, Program and Institute Affiliations

Holden Comprehensive Cancer Center

Selected Publications

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Sparks J, Kumar R, Singh M, Wold M, Pandita T, Burgers P.  Human exonuclease 5 is a novel sliding exonuclease required for genome stability.  The Journal of biological chemistry.  2012 December. 287(51):42773-83.
[PubMed]

Lindsey-Boltz L, Reardon J, Wold M, Sancar A.  In vitro analysis of the role of replication protein A (RPA) and RPA phosphorylation in ATR-mediated checkpoint signaling.  The Journal of biological chemistry.  2012 October. 287(43):36123-31.
[PubMed]

Hass C, Lam K, Wold M.  Repair-specific functions of replication protein A.  The Journal of biological chemistry.  2012 February. 287(6):3908-18.
[PubMed]

Hass C, Chen R, Wold M.  Detection of posttranslational modifications of replication protein A.  Methods in molecular biology (Clifton, N.J.).  2012. 922:193-204.
[PubMed]

Neal J, Dang V, Douglas P, Wold M, Lees-Miller S, Meek K.  Inhibition of homologous recombination by DNA-dependent protein kinase requires kinase activity, is titratable, and is modulated by autophosphorylation.  Molecular and cellular biology.  2011 April. 31(8):1719-33.
[PubMed]

Machwe A, Lozada E, Wold M, Li G, Orren D.  Molecular cooperation between the Werner syndrome protein and replication protein A in relation to replication fork blockage.  The Journal of biological chemistry.  2011 February. 286(5):3497-508.
[PubMed]

Choi J, Lindsey-Boltz L, Kemp M, Mason A, Wold M, Sancar A.  Reconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signaling.  Proceedings of the National Academy of Sciences of the United States of America.  2010 August. 107(31):13660-5.
[PubMed]

Hass C, Gakhar L, Wold M.  Functional characterization of a cancer causing mutation in human replication protein A.  Molecular cancer research : MCR.  2010 July. 8(7):1017-26.
[PubMed]

Mason A, Roy R, Simmons D, Wold M.  Functions of alternative replication protein A in initiation and elongation.  Biochemistry.  2010 July. 49(28):5919-28.
[PubMed]

Kemp M, Mason A, Carreira A, Reardon J, Haring S, Borgstahl G, Kowalczykowski S, Sancar A, Wold M.  An alternative form of replication protein a expressed in normal human tissues supports DNA repair.  The Journal of biological chemistry.  2010 February. 285(7):4788-97.
[PubMed]

Date Last Modified: 06/07/2014 - 21:56:23