James A. Borowiec

James A. Borowiec, PhD

Professor, Department of Biochemistry and Molecular Pharmacology

Keywords
cancer, genome integrity, pharmacology, regulation of eukaryotic DNA repair pathways
Summary

Genotoxic stresses that damage the chromosomal DNA or inhibit the progression of a DNA replication fork can lead to instability of the genetic information and hence cause cellular transformation. One key factor that both signals the presence of genotoxic stress and serves to minimize DNA damage is RPA, the eukaryotic single-stranded DNA-binding protein. A focus of our research is to understand the roles of RPA in enhancing genomic stability. A major line of investigation analyzes the functional significance of RPA phosphorylation by checkpoint (e.g., ATR, ATM) and cell-cycle (e.g., cyclin A-Cdk2) kinases under stress conditions. We have recently found that: 1) in interphase cells with DNA damage, RPA phosphorylation is required for efficient DNA repair by homologous recombination; 2) under conditions of DNA replication stress, RPA phosphorylation by ATR stimulates repair DNA synthesis and prevents ssDNA accumulation; and 3) in cells experiencing mitotic DNA damage, mitotic RPA hyper-phosphorylation facilitates release of cells from a damaged mitosis into a 2N G1 phase, thereby increasing cell viability. These studies indicate that the RPA phosphorylation state causes DNA lesions to be channeled into different DNA repair pathways. Ongoing work is establishing the repair and signaling factors regulated by the RPA phosphorylation state.

Phone

212-263-8453

Fax

212-263-8166

Academic office

550 First Avenue, Medical Science Bldg.

3, 359

New York, NY 10016

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Professor, Department of Biochemistry and Molecular Pharmacology

Course Director, Introduction to Molecular Genetics

Director, Research Emergency Management and Enterprise Resilience

PhD from University of California, Los Angeles

Cell Line-Dependent Synergy Between the PARP Inhibitor Veliparib and the Proteasome Inhibitor Bortezomib in the Killing of Myeloma Cells [Meeting Abstract]

Xu, Alex; Mazumder, Amitabha; Borowiec, James A

Blood. 2015 DEC 3; 126(23):?-?

Murphy, Anar K; Fitzgerald, Michael; Ro, Teresa; Kim, Jee Hyun; Rabinowitsch, Ariana I; Chowdhury, Dipanjan; Schildkraut, Carl L; Borowiec, James A

Journal of cell biology. 2014 Aug 18; 206(4):493-507

Bhatt, Purvi; d'Avout, Claire; Kane, Naomi S; Borowiec, James A; Saxena, Anjana

FEBS journal. 2012 Feb; 279(3):370-383

Brocardo, Mariana G; Borowiec, James A; Henderson, Beric R

International journal of biochemistry & cell biology. 2011 Sep; 43(9):1354-1364

Borowiec, James A; Schildkraut, Carl L

Current opinion in cell biology. 2011 Jun; 23(3):284-292

Single molecule analysis demonstrates that RPA phosphorylation is necessary for efficient fork movement during replication stress [Meeting Abstract]

Murphy, A K; Borowiec, J; Schildkraut, C L

Molecular biology of the cell. 2010 Dec 15; 21(24):?-?

Lee, Dong-Hyun; Pan, Yunfeng; Kanner, Shlomo; Sung, Patrick; Borowiec, James A; Chowdhury, Dipanjan

Nature structural & molecular biology. 2010 Mar; 17(3):365-372

Vassin, Vitaly M; Anantha, Rachel William; Sokolova, Elena; Kanner, Shlomo; Borowiec, James A

Journal of cell science. 2009 Nov 15; 122(Pt 22):4070-4080