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Article: MutLα suppresses error-prone DNA mismatch repair and preferentially protects noncoding DNA from mutations.

Kadyrova, Lyudmila Y / Mieczkowski, Piotr A / Kadyrov, Farid A

bioRxiv : the preprint server for biology

2024

Abstract: The DNA mismatch repair (MMR) system promotes genome stability and protects humans from certain types of cancer. Its primary function is the correction of DNA polymerase errors. MutLα is an important eukaryotic MMR factor. We have examined the ... ...

Abstract	The DNA mismatch repair (MMR) system promotes genome stability and protects humans from certain types of cancer. Its primary function is the correction of DNA polymerase errors. MutLα is an important eukaryotic MMR factor. We have examined the contributions of MutLα to maintaining genome stability. We show here that loss of MutLα in yeast increases the genome-wide mutation rate by ~130-fold and generates a genome-wide mutation spectrum that consists of small indels and base substitutions. We also show that loss of yeast MutLα leads to error-prone MMR that produces T>C base substitutions in 5'-ATA-3' sequences. In agreement with this finding, our examination of human whole genome DNA sequencing data has revealed that loss of MutLα in induced pluripotent stem cells triggers error-prone MMR that leads to the formation of T>C mutations in 5'-NTN-3' sequences. Our further analysis has shown that MutLα-independent MMR plays a role in suppressing base substitutions in N
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.01.587563
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Article ; Online: Genome-wide contributions of the MutSα- and MutSβ-dependent DNA mismatch repair pathways to the maintenance of genetic stability in Saccharomyces cerevisiae.

Kadyrova, Lyudmila Y / Mieczkowski, Piotr A / Kadyrov, Farid A

The Journal of biological chemistry

2023 Volume 299, Issue 5, Page(s) 104705

Abstract: The DNA mismatch repair (MMR) system is a major DNA repair system that suppresses both inherited and sporadic cancers in humans. In eukaryotes, the MutSα-dependent and MutSβ-dependent MMR pathways correct DNA polymerase errors. Here, we investigated ... ...

Abstract	The DNA mismatch repair (MMR) system is a major DNA repair system that suppresses both inherited and sporadic cancers in humans. In eukaryotes, the MutSα-dependent and MutSβ-dependent MMR pathways correct DNA polymerase errors. Here, we investigated these two pathways on a whole genome level in Saccharomyces cerevisiae. We found that inactivation of MutSα-dependent MMR increases the genome-wide mutation rate by ∼17-fold and loss of MutSβ-dependent MMR elevates the genome-wide mutation rate by ∼4-fold. We also found that MutSα-dependent MMR does not show a preference for protecting coding or noncoding DNA from mutations, whereas MutSβ-dependent MMR preferentially protects noncoding DNA from mutations. The most frequent mutations in the msh6Δ strain are C>T transitions, whereas 1- to 6-bp deletions are the most common genetic alterations in the msh3Δ strain. Strikingly, MutSα-dependent MMR is more important than MutSβ-dependent MMR for protection from 1-bp insertions, while MutSβ-dependent MMR has a more critical role in the defense against 1-bp deletions and 2- to 6-bp indels. We also determined that a mutational signature of yeast MSH6 loss is similar to mutational signatures of human MMR deficiency. Furthermore, our analysis showed that compared to other 5'-NCN-3' trinucleotides, 5'-GCA-3' trinucleotides are at the highest risk of accumulating C>T transitions at the central position in the msh6Δ cells and that the presence of a G/A base at the -1 position is important for the efficient MutSα-dependent suppression of C>T transitions. Our results highlight key differences between the roles of the MutSα-dependent and MutSβ-dependent MMR pathways.
MeSH term(s)	DNA ; DNA Mismatch Repair ; DNA Repair ; DNA-Binding Proteins/metabolism ; Mutation ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; MutS DNA Mismatch-Binding Protein/genetics ; MutS DNA Mismatch-Binding Protein/metabolism
Chemical Substances	DNA (9007-49-2) ; DNA-Binding Proteins ; MSH6 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; MutS DNA Mismatch-Binding Protein (EC 3.6.1.3)
Language	English
Publishing date	2023-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.104705
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Article: Microfluidic Organ-on-a-Chip Devices for Liver Disease Modeling In Vitro.

Kanabekova, Perizat / Kadyrova, Adina / Kulsharova, Gulsim

Micromachines

2022 Volume 13, Issue 3

Abstract: Mortality from liver disease conditions continues to be very high. As liver diseases manifest and progress silently, prompt measures after diagnosis are essential in the treatment of these conditions. Microfluidic organs-on-chip platforms have ... ...

Abstract	Mortality from liver disease conditions continues to be very high. As liver diseases manifest and progress silently, prompt measures after diagnosis are essential in the treatment of these conditions. Microfluidic organs-on-chip platforms have significant potential for the study of the pathophysiology of liver diseases in vitro. Different liver-on-a-chip microphysiological platforms have been reported to study cell-signaling pathways such as those activating stellate cells within liver diseases. Moreover, the drug efficacy for liver conditions might be evaluated on a cellular metabolic level. Here, we present a comprehensive review of microphysiological platforms used for modelling liver diseases. First, we briefly introduce the concept and importance of organs-on-a-chip in studying liver diseases in vitro, reflecting on existing reviews of healthy liver-on-a-chip platforms. Second, the techniques of cell cultures used in the microfluidic devices, including 2D, 3D, and spheroid cells, are explained. Next, the types of liver diseases (NAFLD, ALD, hepatitis infections, and drug injury) on-chip are explained for a further comprehensive overview of the design and methods of developing liver diseases in vitro. Finally, some challenges in design and existing solutions to them are reviewed.
Language	English
Publishing date	2022-03-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2620864-7
ISSN	2072-666X
ISSN	2072-666X
DOI	10.3390/mi13030428
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Article: What Elevation Makes 2.5D Prints Perceptually Natural?

Kadyrova, Altynay / Pedersen, Marius / Westland, Stephen

Materials (Basel, Switzerland)

2022 Volume 15, Issue 10

Abstract: Elevation plays a considerable role in naturalness perception of 2.5D prints. The necessary level of elevation to make 2.5D prints look perceptually natural may vary from application to application. Therefore, one needs to know the right elevation for ... ...

Abstract	Elevation plays a considerable role in naturalness perception of 2.5D prints. The necessary level of elevation to make 2.5D prints look perceptually natural may vary from application to application. Therefore, one needs to know the right elevation for specific applications to make the prints look perceptually natural. In this work, we investigated what elevation makes 2.5D prints of wood images perceptually natural. We worked with various wood content images such as wooden wicker, wall, roof, and floor. We found that the optimal elevation that makes 2.5D prints of wood images perceptually natural is content-dependent and in a range between 0.3 mm and 0.5 mm. Moreover, we found that the optimal elevation becomes 0.5 mm if we consider images of wood regardless of the wood content. In addition, there was a high correlation between majority of observers on naturalness perception of 2.5D prints of wood images.
Language	English
Publishing date	2022-05-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma15103573
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Article: Effect of Elevation and Surface Roughness on Naturalness Perception of 2.5D Decor Prints.

Kadyrova, Altynay / Pedersen, Marius / Westland, Stephen

Materials (Basel, Switzerland)

2022 Volume 15, Issue 9

Abstract: Naturalness is a complex concept. It can involve a variety of attributes. In this work, we considered the effect of elevation and surface roughness on naturalness perception of 2.5D decor prints for four material categories. We found that elevation has ... ...

Abstract	Naturalness is a complex concept. It can involve a variety of attributes. In this work, we considered the effect of elevation and surface roughness on naturalness perception of 2.5D decor prints for four material categories. We found that elevation has an impact on the naturalness perception of 2.5D decor prints and that it is linked with content. The observers found lower elevation to be more natural for wood and glass 2.5D prints while there was no clear tendency for stone and metal 2.5D prints. We also found the perceptual attributes used for naturalness assessment of 2.5D decor prints. The top five ones are color, roughness, gloss, elevation, and lightness. The obtained findings can be useful for companies that produce 2.5D prints.
Language	English
Publishing date	2022-05-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma15093372
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Article: Bacterial Co-Infections and Antimicrobial Resistance in Patients Hospitalized with Suspected or Confirmed COVID-19 Pneumonia in Kazakhstan.

Lavrinenko, Alyona / Kolesnichenko, Svetlana / Kadyrova, Irina / Turmukhambetova, Anar / Akhmaltdinova, Lyudmila / Klyuyev, Dmitriy

Pathogens (Basel, Switzerland)

2023 Volume 12, Issue 3

Abstract: Our study was carried out to characterize respiratory tract microbiota in patients with "COVID-like pneumonia" in Kazakhstan and analyze differences between COVID-19 positive and negative groups. Sputum samples were collected from hospitalized patients, ≥ ...

Abstract	Our study was carried out to characterize respiratory tract microbiota in patients with "COVID-like pneumonia" in Kazakhstan and analyze differences between COVID-19 positive and negative groups. Sputum samples were collected from hospitalized patients, ≥18 years old, in the three cities in Kazakhstan with the highest COVID-19 burden in July 2020. Isolates were identified by MALDI-TOF MS. Susceptibility testing was performed by disk diffusion. We used SPSS 26 and MedCalc 19 for statistical analysis. Among 209 patients with pneumonia, the median age was 62 years and 55% were male. RT-PCR-confirmed SARS-CoV-2 cases were found in 40% of patients, and 46% had a bacterial co-infection. Co-infection was not associated with SARS-CoV-2 RT-PCR test results, but antibiotic use was. The most frequent bacteria were
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens12030370
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Article: A rare case of hereditary sensory and autonomic neuropathy type II.

Mamytova, Elmira / Jusupova, Asel / Toktomametova, Anara / Karbozova, Kunduz / Kadyrova, Begimay / Vityala, Yethindra / Tagaev, Tugolbai

Clinical case reports

2023 Volume 11, Issue 3, Page(s) e7015

Abstract: We describe the follow-up of a 29-year-old man diagnosed with hereditary sensory and autonomic neuropathy type II, including the different complications that presented since his childhood. Despite efforts to maintain an optimal quality of life, the lack ... ...

Abstract	We describe the follow-up of a 29-year-old man diagnosed with hereditary sensory and autonomic neuropathy type II, including the different complications that presented since his childhood. Despite efforts to maintain an optimal quality of life, the lack of an early diagnosis led to an unfavorable prognosis and life condition.
Language	English
Publishing date	2023-03-02
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.7015
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Article: Use of B-complex vitamins and olfactory training for treating COVID-19-related anosmia.

Vityala, Yethindra / Kadyrova, Aliya / Zhumabaeva, Shirin / Bazarbaeva, Aizhan / Mamatov, Sagynali

Clinical case reports

2021 Volume 9, Issue 11, Page(s) e05069

Abstract: A 42-year-old male patient was diagnosed with coronavirus disease 2019. His symptoms improved 2 weeks after lopinavir therapy (800 mg/day). However, he was subsequently diagnosed with complete anosmia. Magnetic resonance brain imaging showed no ... ...

Abstract	A 42-year-old male patient was diagnosed with coronavirus disease 2019. His symptoms improved 2 weeks after lopinavir therapy (800 mg/day). However, he was subsequently diagnosed with complete anosmia. Magnetic resonance brain imaging showed no abnormalities. We prescribed B-complex vitamins and olfactory training. Forty days later, he recovered.
Language	English
Publishing date	2021-11-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.5069
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Article ; Online: The nuclease activity of DNA2 promotes exonuclease 1-independent mismatch repair.

Kadyrova, Lyudmila Y / Dahal, Basanta K / Gujar, Vaibhavi / Daley, James M / Sung, Patrick / Kadyrov, Farid A

The Journal of biological chemistry

2022 Volume 298, Issue 4, Page(s) 101831

Abstract: The DNA mismatch repair (MMR) system is a major DNA repair system that corrects DNA replication errors. In eukaryotes, the MMR system functions via mechanisms both dependent on and independent of exonuclease 1 (EXO1), an enzyme that has multiple roles in ...

Abstract	The DNA mismatch repair (MMR) system is a major DNA repair system that corrects DNA replication errors. In eukaryotes, the MMR system functions via mechanisms both dependent on and independent of exonuclease 1 (EXO1), an enzyme that has multiple roles in DNA metabolism. Although the mechanism of EXO1-dependent MMR is well understood, less is known about EXO1-independent MMR. Here, we provide genetic and biochemical evidence that the DNA2 nuclease/helicase has a role in EXO1-independent MMR. Biochemical reactions reconstituted with purified human proteins demonstrated that the nuclease activity of DNA2 promotes an EXO1-independent MMR reaction via a mismatch excision-independent mechanism that involves DNA polymerase δ. We show that DNA polymerase ε is not able to replace DNA polymerase δ in the DNA2-promoted MMR reaction. Unlike its nuclease activity, the helicase activity of DNA2 is dispensable for the ability of the protein to enhance the MMR reaction. Further examination established that DNA2 acts in the EXO1-independent MMR reaction by increasing the strand-displacement activity of DNA polymerase δ. These data reveal a mechanism for EXO1-independent mismatch repair.
MeSH term(s)	DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA Mismatch Repair/genetics ; DNA Polymerase III/metabolism ; Humans
Chemical Substances	DNA Polymerase III (EC 2.7.7.7) ; exodeoxyribonuclease I (EC 3.1.11.1) ; DNA Helicases (EC 3.6.4.-) ; DNA2 protein, human (EC 3.6.4.12)
Language	English
Publishing date	2022-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2022.101831
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Article ; Online: Biomarkers of immunothrombosis and polymorphisms of IL2, IL6, and IL10 genes as predictors of the severity of COVID-19 in a Kazakh population.

Yessenbayeva, Assiya / Apsalikov, Bakytbek / Massabayeva, Meruyert / Kazymov, Maksut / Shakhanova, Aizhan / Mussazhanova, Zhanna / Kadyrova, Irina / Aukenov, Nurlan / Shaimardanov, Nurlan

PloS one

2023 Volume 18, Issue 6, Page(s) e0288139

Abstract: Objectives: To study the role of biological markers of immunothrombosis and polymorphisms of cytokine genes IL2, IL6, IL10 and their influence on the severity of COVID-19 in a Kazakh population.: Methods: A total of 301 patients of Kazakh nationality ...

Abstract	Objectives: To study the role of biological markers of immunothrombosis and polymorphisms of cytokine genes IL2, IL6, IL10 and their influence on the severity of COVID-19 in a Kazakh population. Methods: A total of 301 patients of Kazakh nationality with a confirmed diagnosis of COVID-19 participated in the retrospective study, including 142 patients with severe and 159 with a mild course. Single nucleotide polymorphisms IL2R rs1801274, IL6 rs2069840, and IL10 rs1800872 were genotyped by real-time PCR. Activated partial thromboplastin time, normalized ratio, prothrombin index, prothrombin time, fibrinogen prothrombin time, fibrinogen, D-dimer, and C-reactive protein analysis were also conducted. Results: The average age of patients with severe COVID-19 is higher than of patients with mild COVID-19 (p = 0.03). The findings showed that fibrinogen, D-dimer, and C-reactive protein were significantly greater in the group of patients with severe COVID-19 (p = 0.0001). A very strong correlation between the severity of COVID-19 with the D-dimer and C-reactive protein (p = 0.9) (p = 0.02) was found. Conclusion: The results of our study confirm that D-dimer, fibrinogen, and CRP are biomarkers of inflammation and hypercoagulation that serve as predictors of immunothrombosis affecting the severity of COVID-19. D-dimer is also associated with IL10 rs1800872 gene polymorphism in the Kazakh population with severe COVID-19.
MeSH term(s)	Humans ; C-Reactive Protein/genetics ; Thromboinflammation ; Interleukin-10/genetics ; Interleukin-2 ; Interleukin-6/genetics ; Retrospective Studies ; COVID-19/genetics ; Biomarkers ; Fibrinogen/genetics ; Polymorphism, Single Nucleotide ; Hemostatics
Chemical Substances	C-Reactive Protein (9007-41-4) ; Interleukin-10 (130068-27-8) ; Interleukin-2 ; Interleukin-6 ; Biomarkers ; Fibrinogen (9001-32-5) ; Hemostatics ; IL10 protein, human
Language	English
Publishing date	2023-06-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0288139
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