Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Neuronal enhancers are hotspots for DNA single-strand break repair

W. Wu, SE. Hill, WJ. Nathan, J. Paiano, E. Callen, D. Wang, K. Shinoda, N. van Wietmarschen, JM. Colón-Mercado, D. Zong, R. De Pace, HY. Shih, S. Coon, M. Parsadanian, R. Pavani, H. Hanzlikova, S. Park, SK. Jung, PJ. McHugh, A. Canela, C. Chen,...

. 2021 ; 593 (7859) : 440-444. [pub] 20210325

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, Research Support, N.I.H., Intramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22004420

Defects in DNA repair frequently lead to neurodevelopmental and neurodegenerative diseases, underscoring the particular importance of DNA repair in long-lived post-mitotic neurons1,2. The cellular genome is subjected to a constant barrage of endogenous DNA damage, but surprisingly little is known about the identity of the lesion(s) that accumulate in neurons and whether they accrue throughout the genome or at specific loci. Here we show that post-mitotic neurons accumulate unexpectedly high levels of DNA single-strand breaks (SSBs) at specific sites within the genome. Genome-wide mapping reveals that SSBs are located within enhancers at or near CpG dinucleotides and sites of DNA demethylation. These SSBs are repaired by PARP1 and XRCC1-dependent mechanisms. Notably, deficiencies in XRCC1-dependent short-patch repair increase DNA repair synthesis at neuronal enhancers, whereas defects in long-patch repair reduce synthesis. The high levels of SSB repair in neuronal enhancers are therefore likely to be sustained by both short-patch and long-patch processes. These data provide the first evidence of site- and cell-type-specific SSB repair, revealing unexpected levels of localized and continuous DNA breakage in neurons. In addition, they suggest an explanation for the neurodegenerative phenotypes that occur in patients with defective SSB repair.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22004420
003      
CZ-PrNML
005      
20220127145251.0
007      
ta
008      
220113s2021 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1038/s41586-021-03468-5 $2 doi
035    __
$a (PubMed)33767446
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Wu, Wei $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
245    10
$a Neuronal enhancers are hotspots for DNA single-strand break repair / $c W. Wu, SE. Hill, WJ. Nathan, J. Paiano, E. Callen, D. Wang, K. Shinoda, N. van Wietmarschen, JM. Colón-Mercado, D. Zong, R. De Pace, HY. Shih, S. Coon, M. Parsadanian, R. Pavani, H. Hanzlikova, S. Park, SK. Jung, PJ. McHugh, A. Canela, C. Chen, R. Casellas, KW. Caldecott, ME. Ward, A. Nussenzweig
520    9_
$a Defects in DNA repair frequently lead to neurodevelopmental and neurodegenerative diseases, underscoring the particular importance of DNA repair in long-lived post-mitotic neurons1,2. The cellular genome is subjected to a constant barrage of endogenous DNA damage, but surprisingly little is known about the identity of the lesion(s) that accumulate in neurons and whether they accrue throughout the genome or at specific loci. Here we show that post-mitotic neurons accumulate unexpectedly high levels of DNA single-strand breaks (SSBs) at specific sites within the genome. Genome-wide mapping reveals that SSBs are located within enhancers at or near CpG dinucleotides and sites of DNA demethylation. These SSBs are repaired by PARP1 and XRCC1-dependent mechanisms. Notably, deficiencies in XRCC1-dependent short-patch repair increase DNA repair synthesis at neuronal enhancers, whereas defects in long-patch repair reduce synthesis. The high levels of SSB repair in neuronal enhancers are therefore likely to be sustained by both short-patch and long-patch processes. These data provide the first evidence of site- and cell-type-specific SSB repair, revealing unexpected levels of localized and continuous DNA breakage in neurons. In addition, they suggest an explanation for the neurodegenerative phenotypes that occur in patients with defective SSB repair.
650    _2
$a 5-methylcytosin $x metabolismus $7 D044503
650    _2
$a buněčné linie $7 D002460
650    _2
$a DNA $x biosyntéza $7 D004247
650    12
$a jednořetězcové zlomy DNA $7 D053904
650    12
$a oprava DNA $7 D004260
650    _2
$a replikace DNA $7 D004261
650    _2
$a zesilovače transkripce $x genetika $7 D004742
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a metylace $7 D008745
650    _2
$a neurony $x metabolismus $7 D009474
650    _2
$a poly(ADP-ribosa)polymerasy $x metabolismus $7 D011065
650    _2
$a sekvenční analýza DNA $7 D017422
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Intramural $7 D052060
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Hill, Sarah E $u National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
700    1_
$a Nathan, William J $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA $u Department of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
700    1_
$a Paiano, Jacob $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
700    1_
$a Callen, Elsa $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
700    1_
$a Wang, Dongpeng $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
700    1_
$a Shinoda, Kenta $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
700    1_
$a van Wietmarschen, Niek $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
700    1_
$a Colón-Mercado, Jennifer M $u National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
700    1_
$a Zong, Dali $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
700    1_
$a De Pace, Raffaella $u Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA
700    1_
$a Shih, Han-Yu $u National Eye Institute, NIH, Bethesda, MD, USA
700    1_
$a Coon, Steve $u Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA
700    1_
$a Parsadanian, Maia $u National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
700    1_
$a Pavani, Raphael $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
700    1_
$a Hanzlikova, Hana $u Department of Genome Dynamics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic $u Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK
700    1_
$a Park, Solji $u Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Cancer Institute, NIH, Bethesda, MD, USA $u NIH Regulome Project, NIH, Bethesda, MD, USA
700    1_
$a Jung, Seol Kyoung $u Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Cancer Institute, NIH, Bethesda, MD, USA $u NIH Regulome Project, NIH, Bethesda, MD, USA
700    1_
$a McHugh, Peter J $u Department of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
700    1_
$a Canela, Andres $u The Hakubi Center for Advanced Research and Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
700    1_
$a Chen, Chongyi $u Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD, USA
700    1_
$a Casellas, Rafael $u Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Cancer Institute, NIH, Bethesda, MD, USA $u NIH Regulome Project, NIH, Bethesda, MD, USA
700    1_
$a Caldecott, Keith W $u Department of Genome Dynamics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic. k.w.caldecott@sussex.ac.uk $u Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK. k.w.caldecott@sussex.ac.uk
700    1_
$a Ward, Michael E $u National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. wardme@nih.gov
700    1_
$a Nussenzweig, André $u Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA. andre_nussenzweig@nih.gov
773    0_
$w MED00003455 $t Nature $x 1476-4687 $g Roč. 593, č. 7859 (2021), s. 440-444
856    41
$u https://pubmed.ncbi.nlm.nih.gov/33767446 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220113 $b ABA008
991    __
$a 20220127145247 $b ABA008
999    __
$a ok $b bmc $g 1751785 $s 1155569
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 593 $c 7859 $d 440-444 $e 20210325 $i 1476-4687 $m Nature $n Nature $x MED00003455
LZP    __
$a Pubmed-20220113

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace