Translesion DNA synthesis in eukaryotes: A one- or two-polymerase affair
- Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061, USA
This extract was created in the absence of an abstract.
Cellular DNA is continually damaged by a plethora of extrinsic and intrinsic sources, including UV light from the sun and reactive oxygen species resulting from aerobic respiration. Although cells possess a variety of repair processes to remove DNA lesions, lesions that escape repair can block the replicational machinery, and there has been little understanding of the mechanisms by which eukaryotic cells overcome such blocks and promote the continuity of the newly replicated DNA strand. The past three years, however, have witnessed phenomenal progress in this area of research, and here we highlight the important findings and major conclusions that have emerged regarding translesion DNA synthesis (TLS) in eukaryotes.
The RAD6-, RAD18-dependent pathways for the replication of damaged DNA
Genetic studies in the yeast Saccharomyces cerevisiae have played a key role in the identification of genes involved in damage bypass and in the elucidation of their roles in this process. Inactivation of the RAD6 or RAD18 genes severely impairs both the error-free and mutagenic modes of damage bypass. Rad6, a ubiquitin-conjugating enzyme, exists in vivo in a complex with Rad18, a DNA-binding protein (Bailly et al. 1994, 1997). Genetic studies have indicated that this complex controls the bypass of UV-damaged DNA via at least three separate pathways (Torres-Ramos et al. 2002): an error-free pathway dependent on the RAD5,MMS2, and UBC13 genes; another error-free pathway dependent on the RAD30 gene; and a third pathway that is mutagenic and dependent on the REV1, REV3, andREV7 genes. Rad5, a member of the Swi–Snf family of proteins, is a DNA-dependent ATPase but shows no DNA helicase activity (Johnson et al. 1994). Mms2 forms a complex with Ubc13, and this ubiquitin-conjugating enzyme complex affects the assembly of polyubiquitin chains linked through lysine 63 (Hofmann and Pickart 1999). Although how Rad5 promotes damage bypass and how ubiquitin conjugation by the Rad6–Rad18 …
