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Article ; Online: Mismatch repair: Choreographing accurate strand excision.

Fishel, Richard

2021 Volume 31, Issue 6, Page(s) R293–R296

Abstract: State-of-the-art genetic and cellular studies uniquely implicate the S. cerevisiae Pms1 endonuclease (human PMS2) and ExoI as the major components that produce and/or maintain the strand-specific nicks that precisely direct mismatch repair. ...

Abstract	State-of-the-art genetic and cellular studies uniquely implicate the S. cerevisiae Pms1 endonuclease (human PMS2) and ExoI as the major components that produce and/or maintain the strand-specific nicks that precisely direct mismatch repair.
MeSH term(s)	DNA Mismatch Repair ; Humans ; MutL Proteins ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	PMS1 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; MutL Proteins (EC 3.6.1.3)
Language	English
Publishing date	2021-03-23
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2021.02.001
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Book ; Online ; E-Book: DNA repair in cancer therapy

Kelley, Mark R. / Fishel, Melissa L.

molecular targets and clinical applications

2016

Author's details	edited by Mark R. Kelley, Melissa L. Fishel
Keywords	Cancer/Gene therapy ; DNA repair
Language	English
Size	1 Online-Ressource (xx, 445 Seiten), Illustrationen
Edition	Second edition
Publisher	Academic Press
Publishing place	St. Louis
Publishing country	United States
Document type	Book ; Online ; E-Book
Note	Includes bibliographical references and index
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT019228695
ISBN	978-0-12-803599-3 ; 9780128035825 ; 0-12-803599-4 ; 012803582X
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Mismatch repair.

Fishel, Richard

The Journal of biological chemistry

2015 Volume 290, Issue 44, Page(s) 26395–26403

Abstract: Highly conserved MutS homologs (MSH) and MutL homologs (MLH/PMS) are the fundamental components of mismatch repair (MMR). After decades of debate, it appears clear that the MSH proteins initiate MMR by recognizing a mismatch and forming multiple ... ...

Abstract	Highly conserved MutS homologs (MSH) and MutL homologs (MLH/PMS) are the fundamental components of mismatch repair (MMR). After decades of debate, it appears clear that the MSH proteins initiate MMR by recognizing a mismatch and forming multiple extremely stable ATP-bound sliding clamps that diffuse without hydrolysis along the adjacent DNA. The function(s) of MLH/PMS proteins is less clear, although they too bind ATP and are targeted to MMR by MSH sliding clamps. Structural analysis combined with recent real-time single molecule and cellular imaging technologies are providing new and detailed insight into the thermal-driven motions that animate the complete MMR mechanism.
MeSH term(s)	Adenosine Triphosphate/genetics ; Adenosine Triphosphate/metabolism ; Animals ; DNA/genetics ; DNA/metabolism ; DNA Mismatch Repair/physiology ; DNA Repair Enzymes/genetics ; DNA Repair Enzymes/metabolism ; Humans ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism
Chemical Substances	Nuclear Proteins ; Adenosine Triphosphate (8L70Q75FXE) ; DNA (9007-49-2) ; DNA Repair Enzymes (EC 6.5.1.-)
Language	English
Publishing date	2015-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.R115.660142
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Article ; Online: Optimisation of the timing of fertilisation assessment for oocytes cultured in standard incubation: lessons learnt from time-lapse imaging of 78 348 embryos.

Barrie, A / Smith, R / Campbell, A / Fishel, S

Human reproduction (Oxford, England)

2021 Volume 36, Issue 11, Page(s) 2840–2847

Abstract: Study question: Using time-lapse data, can the current consensus for the timing of fertilisation assessment of oocytes, cultured in standard incubation, be optimised?: Summary answer: The optimum time to perform fertilisation assessment for oocytes ... ...

Abstract	Study question: Using time-lapse data, can the current consensus for the timing of fertilisation assessment of oocytes, cultured in standard incubation, be optimised? Summary answer: The optimum time to perform fertilisation assessment for oocytes cultured in standard incubation is 16.5 ± 0.5 h post-insemination (hpi), and the current consensus requires modification in order to minimise the chance of fertilisation being missed. What is known already: Time-lapse incubation allows the embryologist to retrospectively review collated images of oocytes and embryos to capture important embryological observations that may otherwise be missed in standard incubation. According to expert consensus, the optimum time to perform the assessment of fertilisation is 17 ± 1 hpi. Study design, size, duration: A retrospective, multicentre analysis utilised data obtained from 54 746 ICSI-derived embryos and 23 602 IVF-derived embryos cultured in time-lapse incubation between January 2011 and November 2019. Participants/materials, setting, methods: Using time-lapse imaging (TLI), the precise time of pronuclei appearance and disappearance was recorded, where applicable, and the number of oocytes with two pronuclei observable during 10 30-min intervals from 15 hpi to 20 hpi was determined. Main results and the role of chance: Between 15 and 17.5 hpi, the average number of oocytes exhibiting normal fertilisation, elicited as two pronuclei, was 98.19% with the highest proportion of oocytes having visible pronuclei at 16-16.5 hpi (98.32%). At 18-18.5 hpi, the number of visible pronuclei reduced to 95.53% and continued to fall to 87.02% at 19.5-20 hpi. Limitations, reasons for caution: The authors' expectation is that these findings are transferable to other settings, however it is possible that, with alternative culture media and incubation environments, calibration of this timing may be required. As data cannot readily be recorded for pronuclear appearance for IVF-derived embryos, it is not possible to determine the optimum time to perform the fertilisation assessment for IVF-derived embryos. Wider implications of the findings: By fine-tuning the time at which fertilisation assessment takes place the accuracy of the assessment can be increased to maximise the number of fertilised oocytes identified, thereby increasing the number of usable embryos for the patient. Without TLI and following current consensus guidelines, over 11% (n = 3000) of oocytes would have been marked as unfertilised within this cohort. Further to this, depending on the time of a standard fertilisation assessment, up to 300 embryos which resulted in live births could have been categorised as unfertilised, as they presented no visible pronuclei at the conventional assessment time-point. Study funding/competing interest(s): A.C. is a minor shareholder in CARE Fertility Limited. Validated algorithmic time-lapse embryo selection is offered to patients at CARE Fertility at an additional charge as an adjuvant treatment option. Trial registration number: N/A.
MeSH term(s)	Female ; Fertilization ; Fertilization in Vitro ; Humans ; Oocytes ; Retrospective Studies ; Time-Lapse Imaging
Language	English
Publishing date	2021-10-03
Publishing country	England
Document type	Journal Article
ZDB-ID	632776-x
ISSN	1460-2350 ; 0268-1161 ; 1477-741X
ISSN (online)	1460-2350
ISSN	0268-1161 ; 1477-741X
DOI	10.1093/humrep/deab209
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Article ; Online: DNA strand breaks and gaps target retroviral intasome binding and integration.

Senavirathne, Gayan / London, James / Gardner, Anne / Fishel, Richard / Yoder, Kristine E

Nature communications

2023 Volume 14, Issue 1, Page(s) 7072

Abstract: Retrovirus integration into a host genome is essential for productive infections. The integration strand transfer reaction is catalyzed by a nucleoprotein complex (Intasome) containing the viral integrase (IN) and the reverse transcribed (RT) copy DNA ( ... ...

Abstract	Retrovirus integration into a host genome is essential for productive infections. The integration strand transfer reaction is catalyzed by a nucleoprotein complex (Intasome) containing the viral integrase (IN) and the reverse transcribed (RT) copy DNA (cDNA). Previous studies suggested that DNA target-site recognition limits intasome integration. Using single molecule Förster resonance energy transfer (smFRET), we show prototype foamy virus (PFV) intasomes specifically bind to DNA strand breaks and gaps. These break and gap DNA discontinuities mimic oxidative base excision repair (BER) lesion-processing intermediates that have been shown to affect retrovirus integration in vivo. The increased DNA binding events targeted strand transfer to the break/gap site without inducing substantial intasome conformational changes. The major oxidative BER substrate 8-oxo-guanine as well as a G/T mismatch or +T nucleotide insertion that typically introduce a bend or localized flexibility into the DNA, did not increase intasome binding or targeted integration. These results identify DNA breaks or gaps as modulators of dynamic intasome-target DNA interactions that encourage site-directed integration.
MeSH term(s)	DNA, Viral/metabolism ; Integrases/metabolism ; Retroviridae/genetics ; Retroviridae/metabolism ; Spumavirus/genetics ; Spumavirus/metabolism ; DNA, Complementary ; Virus Integration
Chemical Substances	DNA, Viral ; Integrases (EC 2.7.7.-) ; DNA, Complementary
Language	English
Publishing date	2023-11-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42641-4
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Article ; Online: Continuous Glucose Monitoring in Pregnancy.

Horgan, Rebecca / Hage Diab, Yara / Fishel Bartal, Michal / Sibai, Baha M / Saade, George

Obstetrics and gynecology

2023 Volume 143, Issue 2, Page(s) 195–203

Abstract: Diabetes mellitus in pregnancy is associated with adverse maternal and neonatal outcomes. Optimal glycemic control is associated with improved outcomes. Continuous glucose monitoring is a less invasive alternative to blood glucose measurements. Two types ...

Abstract	Diabetes mellitus in pregnancy is associated with adverse maternal and neonatal outcomes. Optimal glycemic control is associated with improved outcomes. Continuous glucose monitoring is a less invasive alternative to blood glucose measurements. Two types of continuous glucose monitoring are available in the market: real time and intermittently scanned. Continuous glucose monitoring is gaining popularity and is now recommended by some societies for glucose monitoring in pregnant women. In this review, we discuss the differences between the two types of continuous glucose monitoring, optimal treatment goals, and whether there is an improvement in maternal or neonatal outcomes.
MeSH term(s)	Infant, Newborn ; Pregnancy ; Female ; Humans ; Diabetes Mellitus, Type 1 ; Blood Glucose ; Blood Glucose Self-Monitoring ; Continuous Glucose Monitoring ; Diabetes Mellitus, Type 2 ; Hypoglycemic Agents ; Pregnancy Outcome
Chemical Substances	Blood Glucose ; Hypoglycemic Agents
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	207330-4
ISSN	1873-233X ; 0029-7844
ISSN (online)	1873-233X
ISSN	0029-7844
DOI	10.1097/AOG.0000000000005374
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Article ; Online: Evolutionary advantage of a dissociative search mechanism in DNA mismatch repair.

Crocker, Kyle / London, James / Medina, Andrés / Fishel, Richard / Bundschuh, Ralf

Physical review. E

2021 Volume 103, Issue 5-1, Page(s) 52404

Abstract: Protein complexes involved in DNA mismatch repair diffuse along dsDNA as sliding clamps in order to locate a hemimethylated incision site. They have been observed to use a dissociative mechanism, in which two proteins, while continuously remaining ... ...

Abstract	Protein complexes involved in DNA mismatch repair diffuse along dsDNA as sliding clamps in order to locate a hemimethylated incision site. They have been observed to use a dissociative mechanism, in which two proteins, while continuously remaining attached to the DNA, sometimes associate into a single complex sliding on the DNA and sometimes dissociate into two independently sliding proteins. Here, we study the probability that these complexes locate a given target site via a semi-analytic, Monte Carlo calculation that tracks the association and dissociation of the sliding complexes. We compare such probabilities to those obtained using a nondissociative diffusive scan in the space of physically realistic diffusion constants, hemimethylated site distances, and total search times to determine the regions in which dissociative searching is more or less efficient than nondissociative searching. We conclude that the dissociative search mechanism is advantageous in the majority of the physically realistic parameter space, suggesting that the dissociative search mechanism confers an evolutionary advantage.
MeSH term(s)	DNA Mismatch Repair ; Diffusion
Language	English
Publishing date	2021-07-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.103.052404
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Article: Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy.

Elbanna, May / Chowdhury, Nayela N / Rhome, Ryan / Fishel, Melissa L

Frontiers in oncology

2021 Volume 11, Page(s) 749496

Abstract: In the era of precision medicine, radiation medicine is currently focused on the precise delivery of highly conformal radiation treatments. However, the tremendous developments in targeted therapy are yet to fulfill their full promise and arguably have ... ...

Abstract	In the era of precision medicine, radiation medicine is currently focused on the precise delivery of highly conformal radiation treatments. However, the tremendous developments in targeted therapy are yet to fulfill their full promise and arguably have the potential to dramatically enhance the radiation therapeutic ratio. The increased ability to molecularly profile tumors both at diagnosis and at relapse and the co-incident progress in the field of radiogenomics could potentially pave the way for a more personalized approach to radiation treatment in contrast to the current ''one size fits all'' paradigm. Few clinical trials to date have shown an improved clinical outcome when combining targeted agents with radiation therapy, however, most have failed to show benefit, which is arguably due to limited preclinical data. Several key molecular pathways could theoretically enhance therapeutic effect of radiation when rationally targeted either by directly enhancing tumor cell kill or indirectly through the abscopal effect of radiation when combined with novel immunotherapies. The timing of combining molecular targeted therapy with radiation is also important to determine and could greatly affect the outcome depending on which pathway is being inhibited.
Language	English
Publishing date	2021-10-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.749496
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Article: Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges.

Yoder, Kristine E / Rabe, Anthony J / Fishel, Richard / Larue, Ross C

Frontiers in molecular biosciences

2021 Volume 8, Page(s) 662331

Abstract: Retroviruses are obligate intracellular parasites that must integrate a copy of the viral genome into the host DNA. The integration reaction is performed by the viral enzyme integrase in complex with the two ends of the viral cDNA genome and yields an ... ...

Abstract	Retroviruses are obligate intracellular parasites that must integrate a copy of the viral genome into the host DNA. The integration reaction is performed by the viral enzyme integrase in complex with the two ends of the viral cDNA genome and yields an integrated provirus. Retroviral vector particles are attractive gene therapy delivery tools due to their stable integration. However, some retroviral integration events may dysregulate host oncogenes leading to cancer in gene therapy patients. Multiple strategies to target retroviral integration, particularly to genetic safe harbors, have been tested with limited success. Attempts to target integration may be limited by the multimerization of integrase or the presence of host co-factors for integration. Several retroviral integration complexes have evolved a mechanism of tethering to chromatin via a host protein. Integration host co-factors bind chromatin, anchoring the complex and allowing integration. The tethering factor allows for both close proximity to the target DNA and specificity of targeting. Each retrovirus appears to have distinct preferences for DNA sequence and chromatin features at the integration site. Tethering factors determine the preference for chromatin features, but do not affect the subtle sequence preference at the integration site. The sequence preference is likely intrinsic to the integrase protein. New developments may uncouple the requirement for a tethering factor and increase the ability to redirect retroviral integration.
Language	English
Publishing date	2021-05-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2021.662331
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Article ; Online: Pregnancy outcomes among patients with stage 1 chronic hypertension.

Horgan, Rebecca / Hage Diab, Yara / Bartal, Michal Fishel / Sibai, Baha M / Saade, George

American journal of obstetrics & gynecology MFM

2024 Volume 6, Issue 3, Page(s) 101261

Abstract: In recent years, the American College of Cardiology and the American Heart Association have reduced the thresholds for a hypertension diagnosis among nonpregnant adults. This change has led to more individuals with reproductive potential to be labeled as ...

Abstract	In recent years, the American College of Cardiology and the American Heart Association have reduced the thresholds for a hypertension diagnosis among nonpregnant adults. This change has led to more individuals with reproductive potential to be labeled as being chronically hypertensive, and some were started on antihypertensive medications. When these individuals become pregnant, the obstetrical care provider will have to decide whether to manage them as individuals with chronic hypertensive when only a few years ago they would have been managed as normotensive individuals and when the evidence regarding treatment of these patients during pregnancy is limited. If implemented widely, the management of patients with stage 1 hypertension similar to the traditional chronic hypertension will likely lead to additional maternal and fetal testing, to an increase in hospital admissions, and potentially to unnecessary interventions, such as preterm birth. Our goal was to compile the existing evidence regarding the pregnancy outcomes among patients with stage 1 hypertension to assist providers in their diagnosis and management of this patient group.
MeSH term(s)	Pregnancy ; Adult ; Female ; Humans ; Infant, Newborn ; United States ; Pregnancy Outcome/epidemiology ; Premature Birth/diagnosis ; Premature Birth/epidemiology ; Premature Birth/prevention & control ; Hypertension/diagnosis ; Hypertension/drug therapy ; Hypertension/epidemiology ; Prenatal Care
Language	English
Publishing date	2024-01-26
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2589-9333
ISSN (online)	2589-9333
DOI	10.1016/j.ajogmf.2023.101261
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