Robert Joseph Crouch, Ph.D.

Physiological, Biochemical, and Molecular Genetic Events of Recognition and Resolution of RNA/DNA Hybrids

RNA associated to DNA, either as RNA/DNA duplex or incorporated into the chromosome, is a hazard that needs prompt removal. RNases H are the only enzymes that can hydrolyze both types of RNA structures, and consequently are essential to avoid genome instability. We have been involved in describing the chemical composition of RNases H and how they function. More recently, our attention has been directed to defining how RNases H participate in cellular events. Recently, numerous studies from many labs have highlighted the importance of preventing/removing RNA/DNA hybrids to maintain genome integrity. It has become evident that DNAs containing RNA, either hybridized or covalently bound, are more common than previously thought. Replicating DNA polymerases incorporate ribonucleotides at a high rate, and transcription associated R-loops – that consist of one of the DNA strands annealed to the mRNA while the other DNA strand remains in single stranded form - are created under many cellular conditions. Stable R-loops constitute a challenge to genome stability because they are a barrier to transcription and replication fork progression, stalling replication and causing fork collapse. Also the single strand DNA displaced in the R-loop is very sensitive to breakage and triggers the DNA damage response, leading to double strand breaks (DSB) that are repaired by the homologous recombination pathway.

Dr. Robert Crouch received his Ph.D. from the Biochemistry Division of the Chemistry Department, University of Illinois in 1968. He spent 10 months as an Instructor at the University of Bergen, Norway, before assuming a postdoctoral position with Dr.Raymond Gestland at Cold Spring Harbor Laboratory. In 1971, Dr. Crouch took a position as Senior Staff Fellow in NICHD where he is now Head of the Section on Formation of RNA, DDB, NICHD.