James A Borowiec

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James Borowiec

Professor, Department of Biochemistry and Molecular Pharmacology
Coordinator, Research Emergency Resilience
Course Director, Foundations of Cellular and Molecular Biology Part II

Contact Info

Address
550 First Avenue
New York, NY 10016

212/263-8453
James.Borowiec@nyumc.org

Research 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.

Research Interests

Regulation of eukaryotic DNA repair pathways

Cell Line-Dependent Synergy Between the PARP Inhibitor Veliparib and the Proteasome Inhibitor Bortezomib in the Killing of Myeloma Cells
Xu, Alex; Mazumder, Amitabha; Borowiec, James A. Cell Line-Dependent Synergy Between the PARP Inhibitor Veliparib and the Proteasome Inhibitor Bortezomib in the Killing of Myeloma Cells [Meeting Abstract]. Blood. 2015 DEC 3;126(23):?-? (1989322)

Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate fork recovery
Murphy, Anar K; Fitzgerald, Michael; Ro, Teresa; Kim, Jee Hyun; Rabinowitsch, Ariana I; Chowdhury, Dipanjan; Schildkraut, Carl L; Borowiec, James A. Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate fork recovery. Journal of cell biology. 2014 Aug 11;206(4):493-507 (1131922)

Specific domains of nucleolin interact with Hdm2 and antagonize Hdm2-mediated p53 ubiquitination
Bhatt, Purvi; d'Avout, Claire; Kane, Naomi S; Borowiec, James A; Saxena, Anjana. Specific domains of nucleolin interact with Hdm2 and antagonize Hdm2-mediated p53 ubiquitination. FEBS journal. 2011 Dec 19;279(3):370-383 (149953)

Open Sesame: activating dormant replication origins in the mouse immunoglobulin heavy chain (Igh) locus
Borowiec, James A; Schildkraut, Carl L. Open Sesame: activating dormant replication origins in the mouse immunoglobulin heavy chain (Igh) locus. Current opinion in cell biology. 2011 May 14;23(3):284-292 (134310)

Adenomatous polyposis coli protein regulates the cellular response to DNA replication stress
Brocardo, Mariana G; Borowiec, James A; Henderson, Beric R. Adenomatous polyposis coli protein regulates the cellular response to DNA replication stress. International journal of biochemistry & cell biology. 2011 May 30;43(9):1354-1364 (638772)