A model for transcription-dependent R-loop formation at double-stranded DNA breaks: Implications for their detection and biological effects.

R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. During R-loop formation an RNA strand invades the DNA duplex, displacing the homologous DNA strand and binding the complementary DNA strand. Here we analyze a model for transcription-dependent R-loop formation at double-stranded DNA breaks (DSBs).

Evelyn M. Witkin (1921-2023).

Pioneer of cell mutagenesis and DNA repair research.

Unbalanced Growth, the DNA Replication Cycle and Discovery of Repair Replication.

This article recounts my graduate research at Yale University (1954-1958) on unbalanced growth in during thymine deprivation or following ultraviolet (UV) irradiation, with early evidence for the repair of UV-induced DNA damage. Follow-up studies in Copenhagen (1958-1960) in the laboratory of Ole Maaløe led to my discovery that the DNA replication cycle can be synchronized by inhibiting protein and RNA syntheses and that an RNA synthesis step is essential for initiation of the cycle, but not for its completion. This work set the stage for my subsequent research at Stanford University, where the repair replication of damaged DNA was documented, to provide compelling evidence for an excision-repair pathway.

Topology and kinetics of R-loop formation.

R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. They can be formed upon "invasion" of an RNA strand into a DNA duplex, during which the RNA displaces the homologous DNA strand and binds the complementary strand. R-loops have many significant beneficial or deleterious biological effects, so it is important to understand the mechanisms for their generation and processing.