Precise genome duplication requires accurate copying by DNA polymerases and the elimination of occasional mistakes by proofreading exonucleases and mismatch repair enzymes. The commonly held belief that 'if something is worth doing, then it's worth doing well' normally applies to DNA replication and repair, however, there are exceptions. This review describes elements that are crucial to cell fitness, evolution and survival in the recently discovered error-prone DNA polymerases. Large numbers of errant DNA polymerases, spanning microorganisms to humans, are used to rescue stalled replication forks by copying damaged DNA and even undamaged DNA to generate 'purposeful' mutations that generate genetic diversity in times of stress. Here we focus on low-fidelity polymerases from bacteria, comparing Escherichia coli, archeabacteria and those most recently discovered in Gram-positive Bacilli, Streptococcus, pathogenic Mycobacterium and intein-containing cyanobacteria.
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http://dx.doi.org/10.1016/j.tim.2004.04.004 | DOI Listing |
In Saccharomyces cerevisiae cells, the bulk of mitochondrial DNA (mtDNA) replication is mediated by the replicative high-fidelity DNA polymerase γ. However, upon UV irradiation low-fidelity translesion polymerases: Polη, Polζ and Rev1, participate in an error-free replicative bypass of UV-induced lesions in mtDNA. We analysed how translesion polymerases could function in mitochondria.
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December 2024
Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, NHO Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555, Japan.
In order to elucidate novel actions of degalactosylated whey protein (D-WP) in comparison with intact whey protein (WP), the effects of oral intake of D-WP on peripheral blood telomere length and telomerase were examined in young and aged mice. In young mice, peripheral blood telomere length was significantly elongated following oral intake of D-WP for 4 weeks. mRNA expression of both telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) was significantly increased in the peripheral blood following oral intake of D-WP for 4 weeks.
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December 2024
Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
Hypomethylating agents (HMAs) such as azacytidine and decitabine are FDA-approved chemotherapy drugs for hematologic malignancy. By inhibiting DNA methyltransferases, HMAs reactivate tumor suppressor genes (TSGs) and endogenous double-stranded RNAs (dsRNAs) that limit tumor growth and trigger apoptosis via viral mimicry. Yet, HMAs show limited effects in many solid tumors despite the strong induction of TSGs and dsRNAs.
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October 2024
Department of Biology, Tufts University, 200 Boston Ave., Medford, MA 02155, USA.
H-DNA is an intramolecular DNA triplex formed by homopurine/homopyrimidine mirror repeats. Since its discovery, the field has advanced from characterizing the structure to discovering its existence and role . H-DNA interacts with cellular machinery in unique ways, stalling DNA and RNA polymerases and causing genome instability.
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December 2024
Division of Endocrinology, Mayo Clinic, Jacksonville, FL, United States.
Introduction: BRAFV600E mutation (BRAF) is common in papillary thyroid cancer (PTC), and most patients have an excellent outcome. However, a TERT-promoter mutation (pTERT) in the presence of BRAF (BRAFpTERT) has been demonstrated to confer a more aggressive behavior to PTC. Lymphocytic infiltration is often present in PTC.
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