DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner

Patrick L. Collins, Caitlin Purman, Sofia I. Porter, Vincent Nganga, Ankita Saini, Katharina E. Hayer, Greer L. Gurewitz, Barry P. Sleckman, Jeffrey J. Bednarski, Craig H. Bassing and Eugene M. Oltz ()
Additional contact information
Patrick L. Collins: The Ohio State University
Caitlin Purman: Washington University School of Medicine
Sofia I. Porter: The Ohio State University
Vincent Nganga: The Ohio State University
Ankita Saini: The Ohio State University
Katharina E. Hayer: Children’s Hospital of Philadelphia
Greer L. Gurewitz: Washington University School of Medicine
Barry P. Sleckman: University of Alabama at Birmingham
Jeffrey J. Bednarski: Washington University School of Medicine
Craig H. Bassing: Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania
Eugene M. Oltz: The Ohio State University

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Efficient repair of DNA double-strand breaks (DSBs) requires a coordinated DNA Damage Response (DDR), which includes phosphorylation of histone H2Ax, forming γH2Ax. This histone modification spreads beyond the DSB into neighboring chromatin, generating a DDR platform that protects against end disassociation and degradation, minimizing chromosomal rearrangements. However, mechanisms that determine the breadth and intensity of γH2Ax domains remain unclear. Here, we show that chromosomal contacts of a DSB site are the primary determinants for γH2Ax landscapes. DSBs that disrupt a topological border permit extension of γH2Ax domains into both adjacent compartments. In contrast, DSBs near a border produce highly asymmetric DDR platforms, with γH2Ax nearly absent from one broken end. Collectively, our findings lend insights into a basic DNA repair mechanism and how the precise location of a DSB may influence genome integrity.

Date: 2020
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DOI: 10.1038/s41467-020-16926-x

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