4.6 Review

Telomere Fragility and MiDAS: Managing the Gaps at the End of the Road

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Biochemistry & Molecular Biology

Exploiting replication gaps for cancer therapy

Ke Cong et al.

Summary: Defects in DNA double-strand break repair, such as BRCA1 or BRCA2 mutations, make tumors selectively sensitive to PARP inhibitors. However, BRCA and PARP1 also share functions in DNA synthesis on the lagging strand, suggesting that BRCA deficiency may be due to an inherent problem in lagging strand synthesis.

MOLECULAR CELL (2022)

Review Biochemistry & Molecular Biology

Consequences of telomere replication failure: the other end-replication problem

Kirsten A. Brenner et al.

Summary: Telomeres are protective structures at the ends of chromosomes, but they can cause obstacles during replication. Replication stress triggers telomere repair mechanisms, which are error prone and primarily used in tumorigenic contexts. Research suggests that fragile telomeres are ultimately tumor-suppressive and may not require repair.

TRENDS IN BIOCHEMICAL SCIENCES (2022)

Article Cell Biology

MutSβ regulates G4-associated telomeric R-loops to maintain telomere integrity in ALT cancer cells

Despoina Sakellariou et al.

Summary: The study reveals that the mismatch repair protein MutS beta is enriched at telomeres in ALT cancer cells, preventing the accumulation of G-quadruplex (G4) structures and R-loops, thus maintaining telomere integrity during alternative lengthening of telomeres.

CELL REPORTS (2022)

Review Biochemistry & Molecular Biology

Telomeric replication stress: the beginning and the end for alternative lengthening of telomeres cancers

Robert Lu et al.

Summary: Telomeres are protein structures that cover the ends of chromosomes. The DNA at telomeres contains repetitive sequences that are difficult to replicate. Structural abnormalities at ALT telomeres increase replication stress, leading to stalling and collapse of replication forks. This DNA damage stimulates recombination-mediated repair and break-induced telomere synthesis. The coordination between replication stress and DNA repair regulates telomere length in ALT cells, and can be manipulated experimentally. Inducing replication stress may selectively disrupt the viability of ALT cancer cells.

OPEN BIOLOGY (2022)

Article Biochemistry & Molecular Biology

Telomeric 8-oxo-guanine drives rapid premature senescence in the absence of telomere shortening

Ryan P. Barnes et al.

Summary: This study reveals how oxidative stress induces significant cellular aging by generating oxidative damage at telomeres. The mechanism through which oxidative damage triggers cellular senescence is not through telomere shortening, but through inducing telomere fragility, leading to accelerated cellular aging.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2022)

Article Multidisciplinary Sciences

XPF activates break-induced telomere synthesis

Chia-Yu Guh et al.

Summary: This study investigates the role of Telomeric Repeat-Containing RNA (TERRA) in the Alternative Lengthening of Telomeres (ALT) mechanism. The depletion of TERRA has been shown to reduce ALT-associated PML bodies, telomere clustering, and telomere lengthening. TERRA interacts with DNA repair proteins, particularly the endonuclease XPF, to activate the DNA damage response (DDR) and induce break-induced telomere synthesis and lengthening. These findings reveal the mechanisms underlying the initiation and maintenance of ALT.

NATURE COMMUNICATIONS (2022)

Review Oncology

Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies

Jixuan Gao et al.

Summary: This review discusses the latest developments and strategies in targeting telomerase and ALT mechanisms for cancer treatment. It also introduces the methods for detecting these two mechanisms and their utility in clinical diagnosis. In addition to inhibiting telomere maintenance, exploiting the weaknesses of telomeres themselves can induce cell death.

NATURE REVIEWS CANCER (2022)

Article Biochemistry & Molecular Biology

CUL2LRR1, TRAIP and p97 control CMG helicase disassembly in the mammalian cell cycle

Fabrizio Villa et al.

Summary: The disassembly of the eukaryotic replisome is regulated by a conserved pair of ubiquitin ligases, CUL2(LRR1) and TRAIP, in mammals. CUL2(LRR1) ubiquitylates the CMG-MCM7 subunit during S-phase leading to disassembly, while TRAIP activates an alternative disassembly pathway during mitosis.

EMBO REPORTS (2021)

Review Cell Biology

Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization

Ci Ji Lim et al.

Summary: The recently determined structures of telomere maintenance protein complexes shed new light on the regulation of telomere DNA replication and end-capping, and how mutations in their encoding genes may affect their functions. Dysfunctional telomere maintenance can lead to diseases, highlighting the importance of understanding telomere biology for human health.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

Article Cell Biology

Anti-recombination function of MutSα restricts telomere extension by ALT-associated homology-directed repair

Jonathan Barroso-Gonzalez et al.

Summary: Alternative lengthening of telomeres (ALT) is a telomere-elongation mechanism observed in 15% of cancer subtypes. Disruption of the MutSa DNA mismatch repair complex leads to striking telomere hyperextension in ALT cells. MutSa is specifically recruited to telomeres in ALT cells by associating with the PCNA subunit of the replisome, counteracting the role of BLM helicase in stabilizing hyper-extended telomeres and maintaining the survival of MutSa-deficient ALT cancer cells.

CELL REPORTS (2021)

Article Cell Biology

ALT neuroblastoma chemoresistance due to telomere dysfunction-induced ATM activation is reversible with ATM inhibitor AZD0156

Balakrishna Koneru et al.

Summary: Cancers overcome replicative immortality by activating either telomerase or an alternative lengthening of telomeres (ALT) mechanism. ALT neuroblastoma cells exhibit de novo resistance to temozolomide + irinotecan, which may be linked to constitutive ataxia-telangiectasia mutated (ATM) activation. ATM inhibition with AZD0156 shows promise in reversing chemotherapy resistance in ALT neuroblastoma.

SCIENCE TRANSLATIONAL MEDICINE (2021)

Article Multidisciplinary Sciences

BRCA1 binds TERRA RNA and suppresses R-Loop-based telomeric DNA damage

Jekaterina Vohhodina et al.

Summary: The research demonstrates that BRCA1 binds TERRA RNA in an R-loop- and cell cycle-dependent manner, represses its transcription, prevents R-loop-associated damage, and promotes repair to maintain telomere stability.

NATURE COMMUNICATIONS (2021)

Editorial Material Cell Biology

The Heritability of Replication Problems

Jean-Sebastien Hoffmann

Summary: The major challenge in DNA replication is to ensure the transmission of intact genetic material to daughter cells. Despite extensive research on the cellular responses to replication problems and their source, the transmission of genome modifications and their heritability in mitosis has been less documented. Recent studies have shown that low replication stress can impact the next generation of cells, transmitting DNA damage and altering the replication timing program of chromosomal domains in daughter cells. This progression of replication issues into mitosis and daughter cells may provide advantages by alerting cells to risky loci and offering an adaptive mechanism to anticipate future problems, especially in the context of cancer cell resistance to therapy.
Article Cell Biology

CSB cooperates with SMARCAL1 to maintain telomere stability in ALT cells

Emily Feng et al.

JOURNAL OF CELL SCIENCE (2020)

Review Biochemistry & Molecular Biology

G-Quadruplexes at Telomeres: Friend or Foe?

Tracy M. Bryan

MOLECULES (2020)

Article Cell Biology

Break-induced replication promotes fragile telomere formation

Zhe Yang et al.

GENES & DEVELOPMENT (2020)

Article Cell Biology

RTEL1 Regulates G4/R-Loops to Avert Replication-Transcription Collisions

Panagiotis Kotsantis et al.

CELL REPORTS (2020)

Article Biochemistry & Molecular Biology

Brca2 abrogation engages with the alternative lengthening of telomeres via break-induced replication

Mi-Sun Kwon et al.

FEBS JOURNAL (2019)

Article Multidisciplinary Sciences

SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability

Eleonora Petti et al.

NATURE COMMUNICATIONS (2019)

Article Oncology

Mitotic DNA Synthesis Is Differentially Regulated between Cancer and Noncancerous Cells

Cari L. Graber-Feesl et al.

MOLECULAR CANCER RESEARCH (2019)

Article Biochemistry & Molecular Biology

Targeted and Persistent 8-Oxoguanine Base Damage at Telomeres Promotes Telomere Loss and Crisis

Elise Fouquerel et al.

MOLECULAR CELL (2019)

Article Biochemistry & Molecular Biology

Mammalian CST averts replication failure by preventing G-quadruplex accumulation

Miaomiao Zhang et al.

NUCLEIC ACIDS RESEARCH (2019)

Article Multidisciplinary Sciences

The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT)

Robert Lu et al.

NATURE COMMUNICATIONS (2019)

Correction Biochemistry & Molecular Biology

RAD51AP1 Is an Essential Mediator of Alternative Lengthening of Telomeres (vol 76, pg 11, 2019)

Jonathan Barroso-Gonzalez et al.

MOLECULAR CELL (2019)

Article Biochemistry & Molecular Biology

Structural and functional analysis of an OB-fold in human Ctc1 implicated in telomere maintenance and bone marrow syndromes

Prashanth K. Shastrula et al.

NUCLEIC ACIDS RESEARCH (2018)

Article Biochemistry & Molecular Biology

Stabilization of Reversed Replication Forks by Telomerase Drives Telomere Catastrophe

Pol Margalef et al.

Review Biochemistry & Molecular Biology

DNA:RNA hybrids at telomeres - when it is better to be out of the (R) loop

Shir Toubiana et al.

FEBS JOURNAL (2018)

Article Biochemistry & Molecular Biology

The BUB3-BUB1 Complex Promotes Telomere DNA Replication

Feng Li et al.

MOLECULAR CELL (2018)

Review Genetics & Heredity

Break-Induced Replication: The Where, The Why, and The How

J. Kramara et al.

TRENDS IN GENETICS (2018)

Review Genetics & Heredity

Shelterin-Mediated Telomere Protection

Titia de Lange

ANNUAL REVIEW OF GENETICS, VOL 52 (2018)

Article Biochemistry & Molecular Biology

Alternative Lengthening of Telomeres Mediated by Mitotic DNA Synthesis Engages Break-Induced Replication Processes

Jaewon Min et al.

MOLECULAR AND CELLULAR BIOLOGY (2017)

Article Biochemistry & Molecular Biology

Aurora Kinase B, a novel regulator of TERF1 binding and telomeric integrity

Foong Lyn Chan et al.

NUCLEIC ACIDS RESEARCH (2017)

Article Multidisciplinary Sciences

FANCM, BRCA1, and BLM cooperatively resolve the replication stress at the ALT telomeres

Xiaolei Pan et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

Article Biochemistry & Molecular Biology

TERRA promotes telomerase-mediated telomere elongation in Schizosaccharomyces pombe

Martin Moravec et al.

EMBO REPORTS (2016)

Article Biochemistry & Molecular Biology

FANCD2 limits BLM-dependent telomere instability in the alternative lengthening of telomeres pathway

Heather Root et al.

HUMAN MOLECULAR GENETICS (2016)

Article Biochemistry & Molecular Biology

FANCD2 Facilitates Replication through Common Fragile Sites

Advaitha Madireddy et al.

MOLECULAR CELL (2016)

Article Biochemistry & Molecular Biology

RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress

Rahul Bhowmick et al.

MOLECULAR CELL (2016)

Article Multidisciplinary Sciences

Break-induced telomere synthesis underlies alternative telomere maintenance

Robert L. Dilley et al.

NATURE (2016)

Article Biochemistry & Molecular Biology

G-quadruplexes and helicases

Oscar Mendoza et al.

NUCLEIC ACIDS RESEARCH (2016)

Article Cell Biology

Telomere Replication Stress Induced by POT1 Inactivation Accelerates Tumorigenesis

Alexandra M. Pinzaru et al.

CELL REPORTS (2016)

Article Biochemistry & Molecular Biology

Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand

Daniel C. Teasley et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2015)

Article Biochemistry & Molecular Biology

TRF2 Recruits RTEL1 to Telomeres in S Phase to Promote T-Loop Unwinding

Grzegorz Sarek et al.

MOLECULAR CELL (2015)

Article Multidisciplinary Sciences

Replication stress activates DNA repair synthesis in mitosis

Sheroy Minocherhomji et al.

NATURE (2015)

Article Multidisciplinary Sciences

Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors

Rachel Litman Flynn et al.

SCIENCE (2015)

Article Multidisciplinary Sciences

Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX

David Clynes et al.

NATURE COMMUNICATIONS (2015)

Review Cell Biology

Causes and consequences of replication stress

Michelle K. Zeman et al.

NATURE CELL BIOLOGY (2014)

Article Biochemistry & Molecular Biology

NuRD-ZNF827 recruitment to telomeres creates a molecular scaffold for homologous recombination

Dimitri Conomos et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2014)

Article Multidisciplinary Sciences

RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells

Rajika Arora et al.

NATURE COMMUNICATIONS (2014)

Article Biochemistry & Molecular Biology

Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity

Weiqiang Lin et al.

EMBO JOURNAL (2013)

Article Cell Biology

MUS81 promotes common fragile site expression

Songmin Ying et al.

NATURE CELL BIOLOGY (2013)

Article Biochemistry & Molecular Biology

DNA polymerase δ stalls on telomeric lagging strand templates independently from G-quadruplex formation

Justin D. Lormand et al.

NUCLEIC ACIDS RESEARCH (2013)

Article Multidisciplinary Sciences

Break-induced replication occurs by conservative DNA synthesis

Roberto A. Donnianni et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Article Cell Biology

Localization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres

Jamie S. J. Wilson et al.

CELL REPORTS (2013)

Article Oncology

TERRA, hnRNP A1, and DNA-PKcs inte telomeres

Phuong N. Le et al.

FRONTIERS IN ONCOLOGY (2013)

Article Biochemistry & Molecular Biology

RTEL1 Dismantles T Loops and Counteracts Telomeric G4-DNA to Maintain Telomere Integrity

Jean-Baptiste Vannier et al.

Article Biochemistry & Molecular Biology

Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions

Anitha Suram et al.

EMBO JOURNAL (2012)

Article Biochemistry & Molecular Biology

The Breast Cancer Susceptibility Gene BRCA2 Is Required for the Maintenance of Telomere Homeostasis

Jaewon Min et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

Article Biochemistry & Molecular Biology

RECQL4, the Protein Mutated in Rothmund-Thomson Syndrome, Functions in Telomere Maintenance

Avik K. Ghosh et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

Article Multidisciplinary Sciences

TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA

Rachel Litman Flynn et al.

NATURE (2011)

Article Biochemistry & Molecular Biology

FEN1 Ensures Telomere Stability by Facilitating Replication Fork Re-initiation

Abhishek Saharia et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

Article Biochemistry & Molecular Biology

BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping

Sophie Badie et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2010)

Article Biochemistry & Molecular Biology

ATR contributes to telomere maintenance in human cells

Gaelle Pennarun et al.

NUCLEIC ACIDS RESEARCH (2010)

Article Biochemistry & Molecular Biology

Mammalian Telomeres Resemble Fragile Sites and Require TRF1 for Efficient Replication

Agnel Sfeir et al.

Article Biochemistry & Molecular Biology

TERRA RNA Binding to TRF2 Facilitates Heterochromatin Formation and ORC Recruitment at Telomeres

Zhong Deng et al.

MOLECULAR CELL (2009)

Article Cell Biology

Replication stress induces sister-chromatid bridging at fragile site loci in mitosis

Kok Lung Chan et al.

NATURE CELL BIOLOGY (2009)

Article Multidisciplinary Sciences

Telomeric repeat-containing RNA and RNA surveillance factors at mammalian chromosome ends

Claus M. Azzalin et al.

SCIENCE (2007)

Article Multidisciplinary Sciences

Break-induced replication and telomerase-independent telomere maintenance require Pol32

John R. Lydeard et al.

NATURE (2007)

Article Biochemistry & Molecular Biology

The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins

Patrick Ryan Potts et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2007)

Article Biochemistry & Molecular Biology

The human Tim/Tipin complex coordinates an intra-S checkpoint response to UV that slows replication fork displacement

Keziban Unsal-Kacmaz et al.

MOLECULAR AND CELLULAR BIOLOGY (2007)

Article Biochemistry & Molecular Biology

Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase

Megan van Overbeek et al.

CURRENT BIOLOGY (2006)

Article Biochemistry & Molecular Biology

POT1 protects telomeres from a transient DNA damage response and determines how human chromosomes end

D Hockemeyer et al.

EMBO JOURNAL (2005)

Article Biochemistry & Molecular Biology

The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis

DJ Stavropoulos et al.

HUMAN MOLECULAR GENETICS (2002)