The consequences of cohesin mutations in myeloid malignancies
Recurrent somatic mutations in the genes encoding the chromatin-regulatory cohesin complex and its modulators occur in a wide range of human malignancies including a high frequency in myeloid neoplasms. The cohesin complex has a ring-like structure which can enclose two strands of DNA. A first funct...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1319804/full |
| _version_ | 1797614256391192576 |
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| author | Shubhra Ashish Bhattacharya Shubhra Ashish Bhattacharya Eve Dias Eve Dias Andrea Nieto-Aliseda Marcus Buschbeck Marcus Buschbeck |
| author_facet | Shubhra Ashish Bhattacharya Shubhra Ashish Bhattacharya Eve Dias Eve Dias Andrea Nieto-Aliseda Marcus Buschbeck Marcus Buschbeck |
| author_sort | Shubhra Ashish Bhattacharya |
| collection | DOAJ |
| description | Recurrent somatic mutations in the genes encoding the chromatin-regulatory cohesin complex and its modulators occur in a wide range of human malignancies including a high frequency in myeloid neoplasms. The cohesin complex has a ring-like structure which can enclose two strands of DNA. A first function for the complex was described in sister chromatid cohesion during metaphase avoiding defects in chromosome segregation. Later studies identified additional functions of the cohesin complex functions in DNA replication, DNA damage response, 3D genome organisation, and transcriptional regulation through chromatin looping. In this review, we will focus on STAG2 which is the most frequently mutated cohesin subunit in myeloid malignancies. STAG2 loss of function mutations are not associated with chromosomal aneuploidies or genomic instability. We hypothesize that this points to changes in gene expression as disease-promoting mechanism and summarize the current state of knowledge on affected genes and pathways. Finally, we discuss potential strategies for targeting cohesion-deficient disease cells. |
| first_indexed | 2024-03-11T07:07:04Z |
| format | Article |
| id | doaj.art-f3bea6c1a41c4c3a8e68ac2069895386 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-11T07:07:04Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-f3bea6c1a41c4c3a8e68ac20698953862023-11-17T08:55:54ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-11-011010.3389/fmolb.2023.13198041319804The consequences of cohesin mutations in myeloid malignanciesShubhra Ashish Bhattacharya0Shubhra Ashish Bhattacharya1Eve Dias2Eve Dias3Andrea Nieto-Aliseda4Marcus Buschbeck5Marcus Buschbeck6Program of Myeloid Neoplasms, Program of Applied Epigenetics, Josep Carreras Leukaemia Research Institute, Badalona, SpainPhD Program of Cell Biology, Autonomous University of Barcelona, Barcelona, SpainProgram of Myeloid Neoplasms, Program of Applied Epigenetics, Josep Carreras Leukaemia Research Institute, Badalona, SpainPhD Program of Cell Biology, Autonomous University of Barcelona, Barcelona, SpainProgram of Myeloid Neoplasms, Program of Applied Epigenetics, Josep Carreras Leukaemia Research Institute, Badalona, SpainProgram of Myeloid Neoplasms, Program of Applied Epigenetics, Josep Carreras Leukaemia Research Institute, Badalona, SpainGermans Trias i Pujol Research Institute (IGTP), Badalona, SpainRecurrent somatic mutations in the genes encoding the chromatin-regulatory cohesin complex and its modulators occur in a wide range of human malignancies including a high frequency in myeloid neoplasms. The cohesin complex has a ring-like structure which can enclose two strands of DNA. A first function for the complex was described in sister chromatid cohesion during metaphase avoiding defects in chromosome segregation. Later studies identified additional functions of the cohesin complex functions in DNA replication, DNA damage response, 3D genome organisation, and transcriptional regulation through chromatin looping. In this review, we will focus on STAG2 which is the most frequently mutated cohesin subunit in myeloid malignancies. STAG2 loss of function mutations are not associated with chromosomal aneuploidies or genomic instability. We hypothesize that this points to changes in gene expression as disease-promoting mechanism and summarize the current state of knowledge on affected genes and pathways. Finally, we discuss potential strategies for targeting cohesion-deficient disease cells.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1319804/fullcohesinSTAG2chromatinmyelodysplastic syndromesacute myeloid leukemia |
| spellingShingle | Shubhra Ashish Bhattacharya Shubhra Ashish Bhattacharya Eve Dias Eve Dias Andrea Nieto-Aliseda Marcus Buschbeck Marcus Buschbeck The consequences of cohesin mutations in myeloid malignancies Frontiers in Molecular Biosciences cohesin STAG2 chromatin myelodysplastic syndromes acute myeloid leukemia |
| title | The consequences of cohesin mutations in myeloid malignancies |
| title_full | The consequences of cohesin mutations in myeloid malignancies |
| title_fullStr | The consequences of cohesin mutations in myeloid malignancies |
| title_full_unstemmed | The consequences of cohesin mutations in myeloid malignancies |
| title_short | The consequences of cohesin mutations in myeloid malignancies |
| title_sort | consequences of cohesin mutations in myeloid malignancies |
| topic | cohesin STAG2 chromatin myelodysplastic syndromes acute myeloid leukemia |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1319804/full |
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