TY - JOUR
T1 - Encounters in Three Dimensions
T2 - How Nuclear Topology Shapes Genome Integrity
AU - Sebastian, Robin
AU - Aladjem, Mirit I.
AU - Oberdoerffer, Philipp
N1 - Funding Information:
We apologize to the many authors who’s work we were unable to cite due to space constraints. We thank M. Seidman for critical reading of the manuscript. MA is supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research (ZIA BC010411).
Funding Information:
This work was supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research (ZIA BC010411 to MA).
Publisher Copyright:
Copyright © 2021 Sebastian, Aladjem and Oberdoerffer.
PY - 2021/10/21
Y1 - 2021/10/21
N2 - Almost 25 years ago, the phosphorylation of a chromatin component, histone H2AX, was discovered as an integral part of the DNA damage response in eukaryotes. Much has been learned since then about the control of DNA repair in the context of chromatin. Recent technical and computational advances in imaging, biophysics and deep sequencing have led to unprecedented insight into nuclear organization, highlighting the impact of three-dimensional (3D) chromatin structure and nuclear topology on DNA repair. In this review, we will describe how DNA repair processes have adjusted to and in many cases adopted these organizational features to ensure accurate lesion repair. We focus on new findings that highlight the importance of chromatin context, topologically associated domains, phase separation and DNA break mobility for the establishment of repair-conducive nuclear environments. Finally, we address the consequences of aberrant 3D genome maintenance for genome instability and disease.
AB - Almost 25 years ago, the phosphorylation of a chromatin component, histone H2AX, was discovered as an integral part of the DNA damage response in eukaryotes. Much has been learned since then about the control of DNA repair in the context of chromatin. Recent technical and computational advances in imaging, biophysics and deep sequencing have led to unprecedented insight into nuclear organization, highlighting the impact of three-dimensional (3D) chromatin structure and nuclear topology on DNA repair. In this review, we will describe how DNA repair processes have adjusted to and in many cases adopted these organizational features to ensure accurate lesion repair. We focus on new findings that highlight the importance of chromatin context, topologically associated domains, phase separation and DNA break mobility for the establishment of repair-conducive nuclear environments. Finally, we address the consequences of aberrant 3D genome maintenance for genome instability and disease.
KW - chromatin
KW - DNA double-strand break repair
KW - genome integrity
KW - nuclear organization
KW - phase separation
KW - replication stress
KW - Topologically Associated Domain
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U2 - 10.3389/fgene.2021.746380
DO - 10.3389/fgene.2021.746380
M3 - Review article
AN - SCOPUS:85118687267
SN - 1664-8021
VL - 12
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 746380
ER -