DNA damage and repair in the hematopoietic system
Although hematopoietic stem cells (HSCs) in the bone marrow are in a state of quiescence, they harbor the self-renewal capacity and the pluripotency to differentiate into mature blood cells when needed, which is key to maintain hematopoietic homeostasis. Importantly, HSCs are characterized by their...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-05-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022053 |
| _version_ | 1797635395381362688 |
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| author | Li Niu Chen Hongzhu Wang Jian |
| author_facet | Li Niu Chen Hongzhu Wang Jian |
| author_sort | Li Niu |
| collection | DOAJ |
| description | Although hematopoietic stem cells (HSCs) in the bone marrow are in a state of quiescence, they harbor the self-renewal capacity and the pluripotency to differentiate into mature blood cells when needed, which is key to maintain hematopoietic homeostasis. Importantly, HSCs are characterized by their long lifespan (e.g., up to <sc>60 months</sc> for mice), display characteristics of aging, and are vulnerable to various endogenous and exogenous genotoxic stresses. Generally, DNA damage in HSCs is endogenous, which is typically induced by reactive oxygen species (ROS), aldehydes, and replication stress. Mammalian cells have evolved a complex and efficient DNA repair system to cope with various DNA lesions to maintain genomic stability. The repair machinery for DNA damage in HSCs has its own characteristics. For instance, the Fanconi anemia (FA)/BRCA pathway is particularly important for the hematopoietic system, as it can limit the damage caused by DNA inter-strand crosslinks, oxidative stress, and replication stress to HSCs to prevent FA occurrence. In addition, HSCs prefer to utilize the classical non-homologous end-joining pathway, which is essential for the V(D)J rearrangement in developing lymphocytes and is involved in double-strand break repair to maintain genomic stability in the long-term quiescent state. In contrast, the base excision repair pathway is less involved in the hematopoietic system. In this review, we summarize the impact of various types of DNA damage on HSC function and review our knowledge of the corresponding repair mechanisms and related human genetic diseases. |
| first_indexed | 2024-03-11T12:20:30Z |
| format | Article |
| id | doaj.art-217a02adc6a14ee69ca3e1a0ddf7d352 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:20:30Z |
| publishDate | 2022-05-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-217a02adc6a14ee69ca3e1a0ddf7d3522023-11-07T00:58:37ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-05-015484785710.3724/abbs.202205320d259ccDNA damage and repair in the hematopoietic systemLi Niu0Chen Hongzhu1Wang Jian2["Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai 200127, China","Shanghai Clinical Research Center for Rare Pediatric Diseases, Shanghai 200127, China"]["Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China"]["Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai 200127, China","Shanghai Clinical Research Center for Rare Pediatric Diseases, Shanghai 200127, China"]Although hematopoietic stem cells (HSCs) in the bone marrow are in a state of quiescence, they harbor the self-renewal capacity and the pluripotency to differentiate into mature blood cells when needed, which is key to maintain hematopoietic homeostasis. Importantly, HSCs are characterized by their long lifespan (e.g., up to <sc>60 months</sc> for mice), display characteristics of aging, and are vulnerable to various endogenous and exogenous genotoxic stresses. Generally, DNA damage in HSCs is endogenous, which is typically induced by reactive oxygen species (ROS), aldehydes, and replication stress. Mammalian cells have evolved a complex and efficient DNA repair system to cope with various DNA lesions to maintain genomic stability. The repair machinery for DNA damage in HSCs has its own characteristics. For instance, the Fanconi anemia (FA)/BRCA pathway is particularly important for the hematopoietic system, as it can limit the damage caused by DNA inter-strand crosslinks, oxidative stress, and replication stress to HSCs to prevent FA occurrence. In addition, HSCs prefer to utilize the classical non-homologous end-joining pathway, which is essential for the V(D)J rearrangement in developing lymphocytes and is involved in double-strand break repair to maintain genomic stability in the long-term quiescent state. In contrast, the base excision repair pathway is less involved in the hematopoietic system. In this review, we summarize the impact of various types of DNA damage on HSC function and review our knowledge of the corresponding repair mechanisms and related human genetic diseases.https://www.sciengine.com/doi/10.3724/abbs.2022053c-NHEJDNA inter-strand crosslinkFA/BRCA pathwayhematopoietic stem celloxidative damagereplication stress |
| spellingShingle | Li Niu Chen Hongzhu Wang Jian DNA damage and repair in the hematopoietic system Acta Biochimica et Biophysica Sinica c-NHEJ DNA inter-strand crosslink FA/BRCA pathway hematopoietic stem cell oxidative damage replication stress |
| title | DNA damage and repair in the hematopoietic system |
| title_full | DNA damage and repair in the hematopoietic system |
| title_fullStr | DNA damage and repair in the hematopoietic system |
| title_full_unstemmed | DNA damage and repair in the hematopoietic system |
| title_short | DNA damage and repair in the hematopoietic system |
| title_sort | dna damage and repair in the hematopoietic system |
| topic | c-NHEJ DNA inter-strand crosslink FA/BRCA pathway hematopoietic stem cell oxidative damage replication stress |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022053 |
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