Myotonic Dystrophy—A Progeroid Disease? DOI Creative Commons
Peter Meinke,

Stefan Hintze,

Sarah Limmer

et al.

Frontiers in Neurology, Journal Year: 2018, Volume and Issue: 9

Published: July 25, 2018

Myotonic dystrophies (DM) are slowly progressing multisystemic disorders caused by repeat expansions in the DMPK or CNBP genes. The involvement DM patients often reflects appearance of accelerated aging. This is partly due to visible features such as cataracts, muscle weakness, and frontal baldness, but there also less obvious like cardiac arrhythmia, diabetes hypogammaglobulinemia. These aging suggest hypothesis that could be a segmental progeroid disease. To identify molecular cause this characteristic we compare clinical "typical" mutations DNA repair nuclear envelope proteins. Furthermore, characterize if premature effect reflected on cellular level investigate overlaps with "classical" disorders. similarities at use primary control cell lines. analysis reveals many syndromes linked envelope. Our comparison both levels argues for qualification disorder.

Language: Английский

Toward understanding genomic instability, mitochondrial dysfunction and aging DOI Open Access
Nima Borhan Fakouri, Yujun Hou,

Tyler G. Demarest

et al.

FEBS Journal, Journal Year: 2018, Volume and Issue: 286(6), P. 1058 - 1073

Published: Sept. 21, 2018

The biology of aging is an area intense research, and many questions remain about how why cell organismal functions decline over time. In mammalian cells, genomic instability mitochondrial dysfunction are thought to be among the primary drivers cellular aging. This review focuses on interrelationship between in cells its relevance age‐related functional at molecular level. importance oxidative stress key DNA damage response pathways discussed, with a special focus poly ( ADP ‐ribose) polymerase 1, whose persistent activation depletes energy reserves, leading dysfunction, loss homeostasis, altered metabolism. Elucidation relationship instability, signaling that connect these pathways/processes keys future research human An important component health preservation mitophagy, this other areas particularly ripe for investigation will discussed.

Language: Английский

Citations

67
Human Exonuclease 1 (EXO1) Regulatory Functions in DNA Replication with Putative Roles in Cancer DOI Open Access
Guido Keijzers, Daniela Bakula, Michael Petr

et al.

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 20(1), P. 74 - 74

Published: Dec. 25, 2018

Human exonuclease 1 (EXO1), a 5′→3′ exonuclease, contributes to the regulation of cell cycle checkpoints, replication fork maintenance, and post replicative DNA repair pathways. These processes are required for resolution stalled or blocked that can lead stress potential collapse fork. Failure restart process result in double-strand breaks, cell-cycle arrest, death, cellular transformation. In this review, we summarize involvement EXO1 replication, pathways, link between cancer.

Language: Английский

Citations

65
Pharmacological boost of DNA damage response and repair by enhanced biogenesis of DNA damage response RNAs DOI Creative Commons
Ubaldo Gioia, Sofia Francia, Matteo Cabrini

et al.

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: April 23, 2019

Abstract A novel class of small non-coding RNAs called DNA damage response (DDRNAs) generated at double-strand breaks (DSBs) in a DROSHA- and DICER-dependent manner has been shown to regulate the (DDR). Similar molecules were also reported guide repair. Here, we show that DDR activation repair can be pharmacologically boosted by acting on such RNAs. Cells treated with enoxacin, compound previously demonstrated augment DICER activity, stronger signalling faster upon exposure ionizing radiations compared vehicle-only cells. Enoxacin stimulates DDRNA production chromosomal DSBs dysfunctional telomeres, which turn promotes 53BP1 accumulation damaged sites, therefore miRNA-independent manner. Increased occupancy lesions induced enoxacin ultimately suppresses homologous recombination, channelling towards more accurate non-homologous end-joining, including post-mitotic primary neurons. Notably, augmented stimulated increases survival cancer cells chemotherapeutic agents.

Language: Английский

Citations

65
Human RecQ Helicases in DNA Double-Strand Break Repair DOI Creative Commons
Huiming Lu, Anthony J. Davis

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Feb. 25, 2021

RecQ DNA helicases are a conserved protein family found in bacteria, fungus, plants, and animals. These play important roles multiple cellular functions, including replication, transcription, repair, telomere maintenance. Humans have five helicases: RECQL1, Bloom syndrome (BLM), Werner helicase (WRN), RECQL4, RECQL5. Defects BLM WRN cause autosomal disorders: (BS) (WS), respectively. Mutations RECQL4 associated with three genetic disorders, Rothmund–Thomson (RTS), Baller–Gerold (BGS), RAPADILINO syndrome. Although no disorders been reported due to loss of RECQL1 or RECQL5, dysfunction either gene is tumorigenesis. Multiple genetically independent pathways evolved that mediate the repair double-strand break (DSB), pivotal each them. The importance DSB supported by observations defective can chromosomal aberrations, genomic instability, senescence, cell death, which ultimately lead premature aging, neurodegeneration, In this review, we will introduce human family, describe detail their provide relevance between diseases.

Language: Английский

Citations

55
Mitophagy and DNA damage signaling in human aging DOI
Mansi Babbar, Sambuddha Basu,

Beimeng Yang

et al.

Mechanisms of Ageing and Development, Journal Year: 2020, Volume and Issue: 186, P. 111207 - 111207

Published: Jan. 7, 2020

Language: Английский

Citations

52
Therapeutic strategies targeting cellular senescence for cancer and other diseases DOI Creative Commons
Xuebing Wang, Takeshi Fukumoto, Ken-ichi Noma

et al.

The Journal of Biochemistry, Journal Year: 2024, Volume and Issue: 175(5), P. 525 - 537

Published: Feb. 15, 2024

Abstract Cellular senescence occurs in response to endogenous or exogenous stresses and is characterized by stable cell cycle arrest, alterations nuclear morphology secretion of proinflammatory factors, referred as the senescence-associated secretory phenotype (SASP). An increase senescent cells associated with development several types cancer aging-related diseases. Therefore, senolytic agents that selectively remove may offer opportunities for developing new therapeutic strategies against such cancers This review outlines inducers general characteristics cells. We also discuss involvement certain Finally, we describe a series their utilization strategies.

Language: Английский

Citations

6
The MCM8/9 complex: A recent recruit to the roster of helicases involved in genome maintenance DOI Creative Commons
Wezley C. Griffin, Michael A. Trakselis

DNA repair, Journal Year: 2019, Volume and Issue: 76, P. 1 - 10

Published: Feb. 5, 2019

Language: Английский

Citations

50
Rare Genetic Diseases with Defects in DNA Repair: Opportunities and Challenges in Orphan Drug Development for Targeted Cancer Therapy DOI Open Access
Sonali Bhattacharjee, Saikat Nandi

Cancers, Journal Year: 2018, Volume and Issue: 10(9), P. 298 - 298

Published: Sept. 1, 2018

A better understanding of mechanistic insights into genes and enzymes implicated in rare diseases provide a unique opportunity for orphan drug development. Advances made identification synthetic lethal relationships between disorder with oncogenes tumor suppressor have brought new anticancer therapeutic opportunities. Additionally, the rapid development small molecule inhibitors against that participate DNA damage response repair has been successful strategy targeted cancer therapeutics. Here, we discuss recent advances our how many disease promoting genome stability. We also summarize latest developments exploiting to uncover biological mechanisms identify interactions discovery are various stages preclinical clinical studies.

Language: Английский

Citations

48
Fight to the bitter end: DNA repair and aging DOI
Yu Chen, Anke Geng, Weina Zhang

et al.

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 64, P. 101154 - 101154

Published: Sept. 22, 2020

Language: Английский

Citations

48
Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach DOI Open Access
Samuele Lodovichi, Tiziana Cervelli, Achille Pellicioli

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(18), P. 6684 - 6684

Published: Sept. 12, 2020

Alterations in DNA repair pathways are one of the main drivers cancer insurgence. Nevertheless, cells more susceptible to damage than normal and they rely on specific functional survive. Thanks advances genome sequencing, we now have a better idea which genes mutated cancers this prompted development inhibitors targeting players involved essential for survival. Currently, pivotal concept is that combining inhibition mechanisms viability depends most promising way treat tumorigenesis. Numerous been developed many them, efficacy has demonstrated either alone or combination with chemo radiotherapy. In review, will analyze principal cell cycle checkpoint focusing how their alterations could predispose cancer, then explore specifically different proteins each pathway, underscoring rationale behind usage and/or exploitation as adjuvants classic therapies help patients clinical outcome.

Language: Английский

Citations

43