RRC ID 35334
Author Ide H, Shoulkamy MI, Nakano T, Miyamoto-Matsubara M, Salem AM.
Title Repair and biochemical effects of DNA-protein crosslinks.
Journal Mutat. Res.
Abstract Genomic DNA is associated with various structural, regulatory, and transaction proteins. The dynamic and reversible association between proteins and DNA ensures the accurate expression and propagation of genetic information. However, various endogenous, environmental, and chemotherapeutic agents induce DNA-protein crosslinks (DPCs), and hence covalently trap proteins on DNA. Since DPCs are extremely large compared to conventional DNA lesions, they probably impair many aspects of DNA transactions such as replication, transcription, and repair due to steric hindrance. Recent genetic and biochemical studies have shed light on the elaborate molecular mechanism by which cells repair or tolerate DPCs. This review summarizes the current knowledge regarding the repair and biochemical effects of the most ubiquitous form of DPCs, which are associated with no flanked DNA strand breaks. In bacteria small DPCs are eliminated by nucleotide excision repair (NER), whereas oversized DPCs are processed by RecBCD-dependent homologous recombination (HR). NER does not participate in the repair of DPCs in mammalian cells, since the upper size limit of DPCs amenable to mammalian NER is smaller than that of bacterial NER. Thus, DPCs are processed exclusively by HR. The reactivation of the stalled replication fork at DPCs by HR seems to involve fork breakage in mammalian cells but not in bacterial cells. In addition, recent proteomic studies have identified the numbers of proteins in DPCs induced by environmental and chemotherapeutic agents. However, it remains largely elusive how DPCs affect replication and transcription at the molecular level. Considering the extremely large nature of DPCs, it is possible that they impede the progression of replication and transcription machineries by mechanisms different from those for conventional DNA lesions. This might also be true for the DNA damage response and signaling mechanism.
Volume 711(1-2)
Pages 113-22
Published 2011-6-3
DOI 10.1016/j.mrfmmm.2010.12.007
PII S0027-5107(10)00327-1
PMID 21185846
MeSH Animals DNA / metabolism DNA Damage* DNA Repair* DNA Replication DNA, Bacterial Eukaryotic Cells Humans Proteins / metabolism* Recombination, Genetic Transcription, Genetic
IF 2.398
Times Cited 40
WOS Category TOXICOLOGY BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY
Resource
Prokaryotes E. coli NA