Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons-Reference-Cited by-同舟云学术

Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons

Published:2021-04-02 Issue:6537 Volume:372 Page:91-94
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Reid Dylan A.¹^ORCID,Reed Patrick J.¹^ORCID,Schlachetzki Johannes C. M.²^ORCID,Nitulescu Ioana I.¹^ORCID,Chou Grace³^ORCID,Tsui Enoch C.¹^ORCID,Jones Jeffrey R.¹^ORCID,Chandran Sahaana⁴,Lu Ake T.⁵^ORCID,McClain Claire A.¹^ORCID,Ooi Jean H.¹^ORCID,Wang Tzu-Wen³^ORCID,Lana Addison J.²^ORCID,Linker Sara B.¹^ORCID,Ricciardulli Anthony S.¹^ORCID,Lau Shong¹^ORCID,Schafer Simon T.¹^ORCID,Horvath Steve⁵⁶^ORCID,Dixon Jesse R.⁴^ORCID,Hah Nasun³^ORCID,Glass Christopher K.²^ORCID,Gage Fred H.¹^ORCID

Affiliation:

1. Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037-1002, USA.

2. Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0651, USA.

3. Next Generation Sequencing Core, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037-1002, USA.

4. Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037-1002, USA.

5. Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

6. Department of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

DNA repair within neurons Humans have only a limited capacity to generate new neurons. These cells thus need to repair errors in the genome. To better understand this process, Reid et al. developed Repair-seq, a method to locate DNA repair within the genome of stem cell–derived neurons. DNA repair hotspots (DRHs) were more likely to occur within specific genomic features such as gene bodies as well as in genomic formations, open chromatin, and active regulatory regions. This method showed that repair was enriched at sites involved in neuronal function and identity. Furthermore, proteomic data indicated that genes in DRHs are enriched in Alzheimer's disease and that DRHs are more active in aging. These observations link neuronal DNA repair to aging and neurodegeneration. Science , this issue p. 91

Funder

NIH Office of the Director

Alzheimer’s Association

Leona M. and Harry B. Helmsley Charitable Trust

JPB Foundation

NIH

American Heart Association/Paul G. Allen Frontiers Group Brain Health & Cognitive Impairment Initiative

Dolby Charitable Trust

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary