Direct Homologous dsDNA–dsDNA Pairing: How, Where, and Why?

Mazur, Alexey K.; Nguyen, Tinh-Suong; Gladyshev, Eugene

doi:10.1016/j.jmb.2019.11.005

Cited by 8 publications

(4 citation statements)

References 64 publications

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“…Moreover, both one-or two-ended DSBs can be repaired through the HR pathway, and in particular, messy DNA breaks with covalently attached proteins can be repaired through HR 169,173 . Compared to NHEJ, HR is more complicated, involving numerous enzymes and proteins, but is more accurate and error free 174 . In summary, HR is slow, requires a template, is highly accurate, is only initiated at the later S and G2 phases, can repair both one-and two-ended breaks, and can repair protein-blocked ends 175,176 .…”

Section: Dna Dsb Repair Pathwaysmentioning

confidence: 99%

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Huang

Zhou

2020

Sig Transduct Target Ther

680

457

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Radiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia-telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.

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Section: Dna Dsb Repair Pathwaysmentioning

confidence: 99%

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Huang

Zhou

2020

Sig Transduct Target Ther

680

457

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“…Identical DNA sequences appear to have an inherent property to self-interact (152). This type of interaction is thought to enable recombination-independent pairing of homologous chromosomes (153).…”

Section: How Do Repetitive Dna Sequences Contribute To Phase Separation?mentioning

confidence: 99%

Phase separation of DNA: From past to present

King

Shakya

2021

Biophysical Journal

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“…How do other DNA-related metabolic processes, besides transcription, take place in the context of the higher order folding of chromatin is also discussed in this JMB issue in a review by Arnould and Legube [28], who present how chromosome organization into TADs may contribute to double-strand break (DSB) signaling and post-damage DNA repair responses. Mazur et al [29] discuss the ability of identical dsDNA molecules to pair in vivo, independently of the homologous recombination machinery. Interestingly, fungi have evolved gene silencing mechanisms that can be taken advantage of to study this phenomenon.…”

Section: Editorial Overviewmentioning

confidence: 99%