Organisms control the specificity and frequency with which they mutate via their complement of proteins. The mismatch repair (MMR) proteins correct errors after they are made. The DNA polymerases of the cell determine the response to damaged DNA which has not been repaired by excision. Polymerase action can be considered as consisting of three main steps: addition of a base, proofreading of the added nucleotide and elongation. Each of these steps is kinetically complex and can be modulated. The modulation accounts for different behaviors of organisms in response to stress. The recent findings of DNA polymerases with properties appropriate for dealing with damaged DNA may help to account for the phenomenon of spontaneous mutation and for the hypermutability associated with immunoglobulin maturation and carcinogenesis.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/s1568-7864(01)00014-3 | DOI Listing |
Nat Chem
January 2025
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
The synthesis of large RNA with precise modifications at specific positions is in high demand for both basic research and therapeutic applications, but efficient methods are limited. Engineered DNA polymerases have recently emerged as attractive tools for RNA labelling, offering distinct advantages over conventional RNA polymerases. Here, through semi-rational designs, we engineered a DNA polymerase variant and used it to precisely incorporate a diverse range of modifications, including base modifications, 2'-ribose modifications and backbone modifications, into desired positions within RNA.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA, USA.
Pseudouridine (Ψ) is an abundant RNA chemical modification that plays critical biological functions. Current Ψ detection methods are limited in identifying Ψs at base-resolution in U-rich sequence contexts, where Ψ occurs frequently. Here we report "Mut-Ψ-seq" that utilizes the classic N-cyclohexyl N'-(2-morpholinoethyl)carbodiimide (CMC) agent and an evolved reverse transcriptase ("RT-1306") for Ψ mapping at base-resolution.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, NO.1800, Lihu avenue, Wuxi 214122, China.
Inducible systems are crucial to metabolic engineering and synthetic biology, enabling organisms that function as biosensors and produce valuable compounds. However, almost all inducible systems are strain-specific, limiting comparative analyses and applications across strains rapidly. This study designed and presented a robust workflow for developing the cross-species inducible system.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
State Key Laboratory of Agricultural Microbiology and College of Life Science and Technology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Shizishan Road No.1, Hongshan District, 430070 Wuhan, China.
Primase-polymerases (PrimPols) play divergent functions from DNA replication to DNA repair in all three life domains. In archaea and bacteria, numerous and diverse PPs are encoded by mobile genetic elements (MGEs) and act as the replicases for their MGEs. However, their varying activities and functions are not fully understood.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Apurinic/apyrimidinic (AP) sites are endogenous DNA lesions widespread in human cells. Having no nucleobases, they are noncoding and promutagenic. AP site repair is generally initiated through strand incision by AP endonuclease 1 (APE1).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!