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Biosketch / Results /

James A Borowiec, Ph.D.

Professor; Deputy Director of Sackler
Department of Biochemistry and Molecular Pharmacology [1]

Contact Info

Address
550 First Avenue
Dept. of Biochemistry Floor 3 Room 359
Medical Science Building
New York, NY 10016

212-263-8453, 212-263-8454
212-263-8166
James.Borowiec@nyumc.org


[3]

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Education

1980-1986 — University of California at Los Angeles, PhD in Biochemistry, Graduate Education
1986-1989 — Memorial Sloan-Kettering Cancer Center with Dr. Jerard Hurwitz, PostDoctoral Training

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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

Research Keywords

cell cycle checkpoints, eukaryotic DNA replication, replication protein A (RPA), nucleolin, p53

Research Documents

Human RPA phosphorylation by ATR stimulates DNA synthesis and prevents ssDNA accumulation during DNA replication stress [8]
RPA phosphorylation facilitates mitotic exit in response to mitotic DNA damage [9]
Sequential and synergistic modification of human RPA stimulates chromosomal DNA repair [10]

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All data from NYU Health Sciences Library Faculty Bibliography — -

Contact:
http://hsl.med.nyu.edu/faculty-bibliography-search [11]

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 Feb;279(3):370-383, FEBS journal
— id: 149953, year: 2012, vol: 279, page: 370, stat: Journal Article,

Open Sesame: activating dormant replication origins in the mouse immunoglobulin heavy chain (Igh) locus
Borowiec, James A; Schildkraut, Carl L
2011 Jun;23(3):284-292, Current opinion in cell biology
— id: 134310, year: 2011, vol: 23, page: 284, stat: Journal Article,

Adenomatous polyposis coli protein regulates the cellular response to DNA replication stress
Brocardo M.G.; Borowiec J.A.; Henderson B.R.
2011 ;43(9):1354-1364, International journal of biochemistry & cell biology
— id: 136528, year: 2011, vol: 43, page: 1354, stat: Journal Article,

A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination
Lee, DH; Pan, YF; Kanner, S; Sung, P; Borowiec, JA; Chowdhury, D
2010 MAR ;17(3):365-U138, Nature structural & molecular biology
— id: 108314, year: 2010, vol: 17, page: 365, stat: Journal Article,

Single molecule analysis demonstrates that RPA phosphorylation is necessary for efficient fork movement during replication stress
Murphy, A K; Borowiec, J; Schildkraut, C L
2010 15 Dec 2010;21(24):-, Molecular biology of the cell
— id: 157729, year: 2010, vol: 21, page: , stat: Journal Article,

Mitotic crisis: the unmasking of a novel role for RPA
Anantha, Rachel William; Borowiec, James A
2009 Feb 1;8(3):357-361, Cell cycle
— id: 95184, year: 2009, vol: 8, page: 357, stat: Journal Article,

Human RPA phosphorylation by ATR stimulates DNA synthesis and prevents ssDNA accumulation during DNA-replication stress
Vassin, Vitaly M; Anantha, Rachel William; Sokolova, Elena; Kanner, Shlomo; Borowiec, James A
2009 Nov 15;122(Pt 22):4070-4080, Journal of cell science
— id: 104802, year: 2009, vol: 122, page: 4070, stat: Journal Article,

RPA phosphorylation facilitates mitotic exit in response to mitotic DNA damage
Anantha, Rachel William; Sokolova, Elena; Borowiec, James A
2008 Sep 2;105(35):12903-12908, Proceedings of the National Academy of Sciences of the United States of America
— id: 87807, year: 2008, vol: 105, page: 12903, stat: Journal Article,

Sequential and synergistic modification of human Replication Factor A stimulates chromosomal DNA repair
Anantha, Rachel W; Vassin, Vitaly M; Borowiec, James A
2007 Dec 7;282(49):35910-35923, Journal of biological chemistry
— id: 74674, year: 2007, vol: 282, page: 35910, stat: Journal Article,

Nucleolin inhibits Hdm2 by multiple pathways leading to p53 stabilization
Saxena, A; Rorie, C J; Dimitrova, D; Daniely, Y; Borowiec, J A
2006 Nov 23;25(55):7274-7288, Oncogene
— id: 69575, year: 2006, vol: 25, page: 7274, stat: Journal Article,

Novel checkpoint response to genotoxic stress mediated by nucleolin-replication protein a complex formation
Kim, Kyung; Dimitrova, Diana D; Carta, Kristine M; Saxena, Anjana; Daras, Mariza; Borowiec, James A
2005 Mar;25(6):2463-2474, Molecular & cellular biology
— id: 48733, year: 2005, vol: 25, page: 2463, stat: Journal Article,

The Toposome: A New Twist on Topoisomerase IIalpha
Borowiec, James A
2004 May;3(5):627-628, Cell cycle
— id: 42686, year: 2004, vol: 3,