The Chromatin Response to Double-Strand DNA Breaks and Their Repair
Cellular DNA is constantly being damaged by numerous internal and external mutagenic factors. Probably the most severe type of insults DNA could suffer are the double-strand DNA breaks (DSBs). They sever both DNA strands and compromise genomic stability, causing deleterious chromosomal aberrations t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/8/1853 |
| _version_ | 1827711090783420416 |
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| author | Radoslav Aleksandrov Rossitsa Hristova Stoyno Stoynov Anastas Gospodinov |
| author_facet | Radoslav Aleksandrov Rossitsa Hristova Stoyno Stoynov Anastas Gospodinov |
| author_sort | Radoslav Aleksandrov |
| collection | DOAJ |
| description | Cellular DNA is constantly being damaged by numerous internal and external mutagenic factors. Probably the most severe type of insults DNA could suffer are the double-strand DNA breaks (DSBs). They sever both DNA strands and compromise genomic stability, causing deleterious chromosomal aberrations that are implicated in numerous maladies, including cancer. Not surprisingly, cells have evolved several DSB repair pathways encompassing hundreds of different DNA repair proteins to cope with this challenge. In eukaryotic cells, DSB repair is fulfilled in the immensely complex environment of the chromatin. The chromatin is not just a passive background that accommodates the multitude of DNA repair proteins, but it is a highly dynamic and active participant in the repair process. Chromatin alterations, such as changing patterns of histone modifications shaped by numerous histone-modifying enzymes and chromatin remodeling, are pivotal for proficient DSB repair. Dynamic chromatin changes ensure accessibility to the damaged region, recruit DNA repair proteins, and regulate their association and activity, contributing to DSB repair pathway choice and coordination. Given the paramount importance of DSB repair in tumorigenesis and cancer progression, DSB repair has turned into an attractive target for the development of novel anticancer therapies, some of which have already entered the clinic. |
| first_indexed | 2024-03-10T17:49:55Z |
| format | Article |
| id | doaj.art-722fe6811ab4491d95c91ff9d6c4b3fc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T17:49:55Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-722fe6811ab4491d95c91ff9d6c4b3fc2023-11-20T09:24:15ZengMDPI AGCells2073-44092020-08-0198185310.3390/cells9081853The Chromatin Response to Double-Strand DNA Breaks and Their RepairRadoslav Aleksandrov0Rossitsa Hristova1Stoyno Stoynov2Anastas Gospodinov3Roumen Tsanev Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 21, 1113 Sofia, BulgariaRoumen Tsanev Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 21, 1113 Sofia, BulgariaRoumen Tsanev Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 21, 1113 Sofia, BulgariaRoumen Tsanev Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 21, 1113 Sofia, BulgariaCellular DNA is constantly being damaged by numerous internal and external mutagenic factors. Probably the most severe type of insults DNA could suffer are the double-strand DNA breaks (DSBs). They sever both DNA strands and compromise genomic stability, causing deleterious chromosomal aberrations that are implicated in numerous maladies, including cancer. Not surprisingly, cells have evolved several DSB repair pathways encompassing hundreds of different DNA repair proteins to cope with this challenge. In eukaryotic cells, DSB repair is fulfilled in the immensely complex environment of the chromatin. The chromatin is not just a passive background that accommodates the multitude of DNA repair proteins, but it is a highly dynamic and active participant in the repair process. Chromatin alterations, such as changing patterns of histone modifications shaped by numerous histone-modifying enzymes and chromatin remodeling, are pivotal for proficient DSB repair. Dynamic chromatin changes ensure accessibility to the damaged region, recruit DNA repair proteins, and regulate their association and activity, contributing to DSB repair pathway choice and coordination. Given the paramount importance of DSB repair in tumorigenesis and cancer progression, DSB repair has turned into an attractive target for the development of novel anticancer therapies, some of which have already entered the clinic.https://www.mdpi.com/2073-4409/9/8/1853DNA damage responsedouble-strand DNA break repairnon-homologous end joininghomologous recombinationchromatin dynamics in DNA repairsynthetic lethality |
| spellingShingle | Radoslav Aleksandrov Rossitsa Hristova Stoyno Stoynov Anastas Gospodinov The Chromatin Response to Double-Strand DNA Breaks and Their Repair Cells DNA damage response double-strand DNA break repair non-homologous end joining homologous recombination chromatin dynamics in DNA repair synthetic lethality |
| title | The Chromatin Response to Double-Strand DNA Breaks and Their Repair |
| title_full | The Chromatin Response to Double-Strand DNA Breaks and Their Repair |
| title_fullStr | The Chromatin Response to Double-Strand DNA Breaks and Their Repair |
| title_full_unstemmed | The Chromatin Response to Double-Strand DNA Breaks and Their Repair |
| title_short | The Chromatin Response to Double-Strand DNA Breaks and Their Repair |
| title_sort | chromatin response to double strand dna breaks and their repair |
| topic | DNA damage response double-strand DNA break repair non-homologous end joining homologous recombination chromatin dynamics in DNA repair synthetic lethality |
| url | https://www.mdpi.com/2073-4409/9/8/1853 |
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