Редактирование: FEN1

Flap endonuclease 1 (EC 3.1.-.-) (FEN-1) (DNase IV) (Flap structure-specific endonuclease 1) (Maturation factor 1) (MF1) (hFEN-1) [RAD2]

==Publications==

{{medline-entry
|title=Impairment of Pol β-related DNA Base-excision Repair Leads to Ovarian Aging in Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33223510
|abstract=The mechanism underlying the association between age and depletion of the human ovarian follicle reserves remains uncertain. Many identified that impaired DNA polymerase β (Pol β)-mediated DNA base-excision repair (BER) drives to mouse oocyte aging. With aging, DNA lesions accumulate in primordial follicles. However, the expression of most DNA BER genes, including APE1, [[OGG1]], [[XRCC1]], Ligase I, Ligase α, [[PCNA]] and [[FEN1]], remains unchanged during aging in mouse oocytes. Also, the reproductive capacity of Pol β /- heterozygote mice was impaired, and the primordial follicle counts were lower than that of wild type (wt) mice. The DNA lesions of heterozygous mice increased. Moreover, the Pol β knockdown leads to increased DNA damage in oocytes and decreased survival rate of oocytes. Oocytes over-expressing Pol β showed that the vitality of senescent cells enhancesis significantly. Furthermore, serum concentrations of anti-Müllerian hormone (AMH) indicated that the ovarian reserves of young mice with Pol β germline mutations were lower than those in wt. These data show that Pol β-related DNA BER efficiency is a major factor governing oocyte aging in mice.

|keywords=* BER
* Pol β
* menopause
* oocytes
* ovarian aging
|full-text-url=https://sci-hub.do/10.18632/aging.104123
}}
{{medline-entry
|title=Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31597307
|abstract=Senescence is defined as a stress-induced durable cell cycle arrest. We herein revisit the origin of two of these stresses, namely mitochondrial metabolic compromise, associated with reactive oxygen species (ROS) production, and replicative senescence, activated by extreme telomere shortening. We discuss how replication stress-induced DNA damage of telomeric DNA (telDNA) and mitochondrial DNA (mtDNA) can be considered a common origin of senescence in vitro, with consequences on ageing in vivo. Unexpectedly, mtDNA and telDNA share common features indicative of a high degree of replicative stress, such as G-quadruplexes, D-loops, RNA:DNA heteroduplexes, epigenetic marks, or supercoiling. To avoid these stresses, both compartments use similar enzymatic strategies involving, for instance, endonucleases, topoisomerases, helicases, or primases. Surprisingly, many of these replication helpers are active at both telDNA and mtDNA (e.g., RNAse H1, [[FEN1]], [[DNA2]], RecQ helicases, Top2α, Top2β, [[TOP3A]], DNMT1/3a/3b, SIRT1). In addition, specialized telomeric proteins, such as [[TERT]] (telomerase reverse transcriptase) and TERC (telomerase RNA component), or TIN2 (shelterin complex), shuttle from telomeres to mitochondria, and, by doing so, modulate mitochondrial metabolism and the production of ROS, in a feedback manner. Hence, mitochondria and telomeres use common weapons and cooperate to resist/prevent replication stresses, otherwise producing common consequences, namely senescence and ageing.
|mesh-terms=* Aging
* Animals
* Cellular Senescence
* DNA Damage
* DNA Replication
* DNA, Mitochondrial
* Epigenesis, Genetic
* Humans
* Mitochondria
* Oxidative Stress
* Stress, Physiological
* Telomere
* Telomere Homeostasis
* Telomere Shortening
|keywords=* G-quadruplex
* R-loop
* ageing
* helicase
* mitochondria
* replication stress
* senescence
* telomere
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801922
}}
{{medline-entry
|title=The Werner Syndrome Helicase Coordinates Sequential Strand Displacement and [[FEN1]]-Mediated Flap Cleavage during Polymerase δ Elongation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27849570
|abstract=The Werner syndrome protein ([[WRN]]) suppresses the loss of telomeres replicated by lagging-strand synthesis by a yet to be defined mechanism. Here, we show that whereas either [[WRN]] or the Bloom syndrome helicase (BLM) stimulates DNA polymerase δ progression across telomeric G-rich repeats, only [[WRN]] promotes sequential strand displacement synthesis and [[FEN1]] cleavage, a critical step in Okazaki fragment maturation, at these sequences. Helicase activity, as well as the conserved winged-helix (WH) motif and the helicase and RNase D C-terminal (HRDC) domain play important but distinct roles in this process. Remarkably, [[WRN]] also influences the formation of [[FEN1]] cleavage products during strand displacement on a nontelomeric substrate, suggesting that [[WRN]] recruitment and cooperative interaction with [[FEN1]] during lagging-strand synthesis may serve to regulate sequential strand displacement and flap cleavage at other genomic sites. These findings define a biochemical context for the physiological role of [[WRN]] in maintaining genetic stability.
|mesh-terms=* Amino Acid Motifs
* DNA
* DNA Polymerase III
* DNA Replication
* Flap Endonucleases
* HeLa Cells
* Homeostasis
* Humans
* Polymerization
* Protein Domains
* RecQ Helicases
* Repetitive Sequences, Nucleic Acid
* Substrate Specificity
* Telomere
* Werner Syndrome Helicase
|keywords=* DNA helicase
* DNA replication
* Okazaki fragment
* Werner syndrome
* aging
* lagging strand
* lagging-strand synthesis
* telomeres
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247617
}}
{{medline-entry
|title=[[RECQL5]] has unique strand annealing properties relative to the other human RecQ helicase proteins.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26717024
|abstract=The RecQ helicases play important roles in genome maintenance and DNA metabolism (replication, recombination, repair, and transcription). Five different homologs are present in humans, three of which are implicated in accelerated aging genetic disorders: Rothmund Thomson (RECQL4), Werner (WRN), and Bloom (BLM) syndromes. While the DNA helicase activities of the 5 human RecQ helicases have been extensively characterized, much less is known about their DNA double strand annealing activities. Strand annealing is an important integral enzymatic activity in DNA metabolism, including DNA repair. Here, we have characterized the strand annealing activities of all five human RecQ helicase proteins and compared them. Interestingly, the relative strand annealing activities of the five RecQ proteins are not directly (inversely) related to their helicase activities. [[RECQL5]] possesses relatively strong annealing activity on long or small duplexed substrates compared to the other RecQs. Additionally, the strand annealing activity of [[RECQL5]] is not inhibited by the presence of ATP, unlike the other RecQs. We also show that [[RECQL5]] efficiently catalyzes annealing of RNA to DNA in vitro in the presence or absence of ATP, revealing a possible new function for [[RECQL5]]. Additionally, we investigate how different known RecQ interacting proteins, RPA, Ku, [[FEN1]] and [[RAD51]], regulate their strand annealing activity. Collectively, we find that the human RecQ proteins possess differential DNA double strand annealing activities and we speculate on their individual roles in DNA repair. This insight is important in view of the many cellular DNA metabolic actions of the RecQ proteins and elucidates their unique functions in the cell. 
|mesh-terms=* Adenosine Triphosphate
* Antigens, Nuclear
* DNA
* DNA Repair
* DNA-Binding Proteins
* Flap Endonucleases
* Humans
* Ku Autoantigen
* Rad51 Recombinase
* RecQ Helicases
* Substrate Specificity
|keywords=* Aging
* DNA repair
* DNA–DNA hybrid
* RNA–DNA hybrid
* RecQ helicase
* Strand annealing
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903426
}}