R-Loops at Chromosome Ends: From Formation, Regulation, and Cellular Consequence

Gong, Yaoqin; Liu, Yie

doi:10.3390/cancers15072178

Cited by 13 publications

(5 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…R-loops can cause replication fork stalling and, as a result, DNA breaks and recombination [32,94]. Telomeric R-loops considerably increase homologous recombination events, as discussed in recent extensive reviews [33,[95][96][97]. Homologous recombination at the telomeres is inhibited by the chromatin remodeling factor ATRX, TERRA RNA-binding proteins NONO and SFPQ, and other factors that suppress R-loop formation, recombination, and DNA damage in mammalian telomeres [59,97,98].…”

Section: Telomeres In Aging: Shortening or Dysfunction?mentioning

confidence: 99%

“…Telomeric R-loops considerably increase homologous recombination events, as discussed in recent extensive reviews [33,[95][96][97]. Homologous recombination at the telomeres is inhibited by the chromatin remodeling factor ATRX, TERRA RNA-binding proteins NONO and SFPQ, and other factors that suppress R-loop formation, recombination, and DNA damage in mammalian telomeres [59,97,98]. Internal telomeric DNA breaks, generated in one way or another, serve as substrates for homologous recombination.…”

Section: Telomeres In Aging: Shortening or Dysfunction?mentioning

confidence: 99%

See 1 more Smart Citation

Telomere Checkpoint in Development and Aging

Kalmykova

2023

IJMS

View full text Add to dashboard Cite

The maintenance of genome integrity through generations is largely determined by the stability of telomeres. Increasing evidence suggests that telomere dysfunction may trigger changes in cell fate, independently of telomere length. Telomeric multiple tandem repeats are potentially highly recombinogenic. Heterochromatin formation, transcriptional repression, the suppression of homologous recombination and chromosome end protection are all required for telomere stability. Genetic and epigenetic defects affecting telomere homeostasis may cause length-independent internal telomeric DNA damage. Growing evidence, including that based on Drosophila research, points to a telomere checkpoint mechanism that coordinates cell fate with telomere state. According to this scenario, telomeres, irrespective of their length, serve as a primary sensor of genome instability that is capable of triggering cell death or developmental arrest. Telomeric factors released from shortened or dysfunctional telomeres are thought to mediate these processes. Here, we discuss a novel signaling role for telomeric RNAs in cell fate and early development. Telomere checkpoint ensures genome stability in multicellular organisms but aggravates the aging process, promoting the accumulation of damaged and senescent cells.

show abstract

Section: Telomeres In Aging: Shortening or Dysfunction?mentioning

confidence: 99%

Section: Telomeres In Aging: Shortening or Dysfunction?mentioning

confidence: 99%

Telomere Checkpoint in Development and Aging

Kalmykova

2023

IJMS

View full text Add to dashboard Cite

show abstract

“…They usually accumulate in specific genome regions, including telomeres, centromeres, and mitochondrial DNA (mtDNA) [5]. R-loops are dynamic structures that are prevalent in the whole genome, accounting for up to 5% of the mammalian genome and present on thousands of copies of mtDNA per cell [15][16][17].…”

Section: R-loops' Formation In Physiological and Pathological Conditionsmentioning

confidence: 99%

R-Loops in Genome Instability and Cancer

Li,

Zafar,

Luo

et al. 2023

Cancers

View full text Add to dashboard Cite

R-loops are unique, three-stranded nucleic acid structures that primarily form when an RNA molecule displaces one DNA strand and anneals to the complementary DNA strand in a double-stranded DNA molecule. R-loop formation can occur during natural processes, such as transcription, in which the nascent RNA molecule remains hybridized with the template DNA strand, while the non-template DNA strand is displaced. However, R-loops can also arise due to many non-natural processes, including DNA damage, dysregulation of RNA degradation pathways, and defects in RNA processing. Despite their prevalence throughout the whole genome, R-loops are predominantly found in actively transcribed gene regions, enabling R-loops to serve seemingly controversial roles. On one hand, the pathological accumulation of R-loops contributes to genome instability, a hallmark of cancer development that plays a role in tumorigenesis, cancer progression, and therapeutic resistance. On the other hand, R-loops play critical roles in regulating essential processes, such as gene expression, chromatin organization, class-switch recombination, mitochondrial DNA replication, and DNA repair. In this review, we summarize discoveries related to the formation, suppression, and removal of R-loops and their influence on genome instability, DNA repair, and oncogenic events. We have also discussed therapeutical opportunities by targeting pathological R-loops.

show abstract

“…T-loops are RNA: DNA hybrids formed between a single RNA strand and a double-stranded DNA. Telomeric repeat containing RNA (TERRA) is transcribed from subtelomeric regions to telomeres and can invade telomeric dsDNA to form telomeric R-loop structures [ 83 ]. The SWI/SNF chromatin remodeling complex plays an important role in resolving R-loop conflicts.…”

Section: Review and Hypothesismentioning

confidence: 99%

Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis

Torres-Montaner

2023

CIMB

View full text Add to dashboard Cite

Contrary to what was once thought, direct cancer originating from normal stem cells seems to be extremely rare. This is consistent with a preneoplastic period of telomere length reduction/damage in committed cells that becomes stabilized in transformation. Multiple observations suggest that telomere damage is an obligatory step preceding its stabilization. During tissue turnover, the telomeres of cells undergoing differentiation can be damaged as a consequence of defective DNA repair caused by endogenous or exogenous agents. This may result in the emergence of new mechanism of telomere maintenance which is the final outcome of DNA damage and the initial signal that triggers malignant transformation. Instead, transformation of stem cells is directly induced by primary derangement of telomere maintenance mechanisms. The newly modified telomere complex may promote survival of cancer stem cells, independently of telomere maintenance. An inherent resistance of stem cells to transformation may be linked to specific, robust mechanisms that help maintain telomere integrity.

show abstract

R-Loops at Chromosome Ends: From Formation, Regulation, and Cellular Consequence

Cited by 13 publications

References 154 publications

Telomere Checkpoint in Development and Aging

Telomere Checkpoint in Development and Aging

R-Loops in Genome Instability and Cancer

Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis

Contact Info

Product

Resources

About