DNA interstrand cross-links are complex lesions that covalently link both strands of the duplex DNA. Lesion removal is proposed to be initiated via the UvrABC nucleotide excision repair complex; however, less is known about the subsequent steps of this complex repair pathway. In this study, we characterized the contribution of nucleotide excision repair mutants to survival in the presence of ps...

Alternative reproductive cycles make use of different strategies to generate different reproductive products. In Escherichia coli, recA and several other rec genes are required for the generation of recombinant genomes during Hfr conjugation. During normal asexual reproduction, many of these same genes are needed to generate clonal products from UV-irradiated cells. However, unlike conjugation,...

DNA interstrand crosslinks (ICLs) formed by antitumor agents, such as cisplatin or mitomycin C, are highly cytotoxic DNA lesions. Their repair is believed to be triggered primarily by the stalling of replication forks at ICLs in S-phase. There is, however, increasing evidence that ICL repair can also occur independently of replication. Using a reporter assay, we describe a pathway for the repai...

Cellular processes such as transcription and DNA repair may be regulated through diverse mechanisms, including RNA synthesis, protein synthesis, posttranslational modification and protein degradation. The 26S proteasome, which is responsible for degrading a broad spectrum of proteins, has been shown to interact with several nucleotide excision repair proteins, including xeroderma pigmentosum B ...

DNA-protein crosslinks are relatively common DNA lesions that form during the physiological processing of DNA by replication and recombination proteins, by side reactions of base excision repair enzymes, and by cellular exposure to bifunctional DNA-damaging agents such as platinum compounds. The mechanism by which pathological DNA-protein crosslinks are repaired in humans is not known. In this ...

The kinetics of DNA repair and RNA synthesis recovery in human cells following UV-irradiation were assessed using nascent RNA Bru-seq and quantitative long PCR. It was found that UV light inhibited transcription elongation and that recovery of RNA synthesis occurred as a wave in the 5'-3' direction with slow recovery and TC-NER at the 3' end of long genes. RNA synthesis resumed fully at the 3'-...

Arsenic is well established as a human carcinogen, but its precise mechanism of action remains unknown. Arsenic does not directly damage DNA, but may act as a carcinogen through inhibition of DNA repair mechanisms, leading indirectly to increased mutations from other DNA damaging agents. The molecular mechanism underlying arsenic inhibition of nucleotide excision repair after UV irradiation (Ha...

Stem cells, one of the progenitors of cancer, exist predominately in a quiescent state. Thus, understanding the mechanisms of DNA repair and mutagenesis in such arrested cells may help unravel the complex process of tumorigenesis. Two major nucleotide excision repair (NER) pathways are known to remove bulky physical or chemical lesions from DNA. Transcription-coupled repair (TCR) acts solely on...

DNA damage from exposure to environmental chemical carcinogens and failure of repair systems to eliminate these lesions from the genome are considered as the crucial initial steps in the development of various human malignancies. Many cellular proteins are known to play vital roles to overcome the effects of DNA damage. Among such proteins, p53 is known to respond to DNA damage by accumulating ...

Exposure to ultraviolet-B radiation impairs cellular immune responses. This immunosuppression seems to be associated with Langerhans cell migration. DNA damage appears to play a key role because enhanced nucleotide excision repair, a pathway essential for elimination of ultraviolet-B-induced DNA lesions, strongly counteracts immunosuppression. To determine the effect of DNA repair on ultraviole...