James A Borowiec

Biosketch / Results /

James A Borowiec, Ph.D.

Department of Biochemistry and Molecular Pharmacology

Contact Info

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

212-263-8453, 212-263-8454

« Back to Results


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

« Back to Results

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