James A Borowiec

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James Borowiec

Professor, Department of Biochemistry and Molecular Pharmacology
Biochemistry and Molecular Pharmacology

Contact Info

550 First Avenue
New York, NY 10016


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

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
2014-08-25; 0021-9525,Journal of cell biology - id: 1131922, year: 2014 Journal Article

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
2012-02-05; 1742-4658,FEBS journal - id: 149953, year: 2012

Open Sesame: activating dormant replication origins in the mouse immunoglobulin heavy chain (Igh) locus
Borowiec, James A; Schildkraut, Carl L
2012-02-05; 1879-0410,Current opinion in cell biology - id: 134310, year: 2011

Adenomatous polyposis coli protein regulates the cellular response to DNA replication stress
Brocardo, Mariana G; Borowiec, James A; Henderson, Beric R
2013-11-22; 1357-2725,International journal of biochemistry & cell biology - id: 638772, year: 2011 Journal Article; Research Support, Non-U.S. Gov't

A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination
Lee, Dong-Hyun; Pan, Yunfeng; Kanner, Shlomo; Sung, Patrick; Borowiec, James A; Chowdhury, Dipanjan
2013-11-22; 1545-9985,Nature structural & molecular biology - id: 638782, year: 2010 Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't