scholarly journals MDC1 Directly Binds Phosphorylated Histone H2AX to Regulate Cellular Responses to DNA Double-Strand Breaks

Cell ◽  
2006 ◽  
Vol 124 (6) ◽  
pp. 1299 ◽  
Author(s):  
Manuel Stucki ◽  
Julie A. Clapperton ◽  
Duaa Mohammad ◽  
Michael B. Yaffe ◽  
Stephen J. Smerdon ◽  
...  
Keyword(s):  
Cellular Responses ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Histone H2ax

scholarly journals MDC1 Directly Binds Phosphorylated Histone H2AX to Regulate Cellular Responses to DNA Double-Strand Breaks

Cell ◽  
2008 ◽  
Vol 133 (3) ◽  
pp. 549 ◽  
Author(s):  
Manuel Stucki ◽  
Julie A. Clapperton ◽  
Duaa Mohammad ◽  
Michael B. Yaffe ◽  
Stephen J. Smerdon ◽  
...  
Keyword(s):  
Cellular Responses ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Histone H2ax

scholarly journals MDC1 Directly Binds Phosphorylated Histone H2AX to Regulate Cellular Responses to DNA Double-Strand Breaks

Cell ◽  
2005 ◽  
Vol 123 (7) ◽  
pp. 1213-1226 ◽  
Author(s):  
Manuel Stucki ◽  
Julie A. Clapperton ◽  
Duaa Mohammad ◽  
Michael B. Yaffe ◽  
Stephen J. Smerdon ◽  
...  
Keyword(s):  
Cellular Responses ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Histone H2ax

scholarly journals MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Israel Salguero ◽  
Rimma Belotserkovskaya ◽  
Julia Coates ◽  
Matylda Sczaniecka-Clift ◽  
Mukerrem Demir ◽  
...  
Keyword(s):  
Dna Damage ◽  
Double Strand Breaks ◽  
Repeat Region ◽  
Independent Function ◽  
Dna Double Strand Breaks ◽  
Dna Damage Tolerance ◽  
Strand Breaks ◽  
Histone H2ax ◽  
Independent Association ◽  
Dna Damage Signalling

AbstractHistone H2AX and MDC1 are key DNA repair and DNA-damage signalling proteins. When DNA double-strand breaks (DSBs) occur, H2AX is phosphorylated and then recruits MDC1, which in turn serves as a docking platform to promote the localization of other factors, including 53BP1, to DSB sites. Here, by using CRISPR-Cas9 engineered human cell lines, we identify a hitherto unknown, H2AX-independent, function of MDC1 mediated by its PST-repeat region. We show that the PST-repeat region directly interacts with chromatin via the nucleosome acidic patch and mediates DNA damage-independent association of MDC1 with chromatin. We find that this region is largely functionally dispensable when the canonical γH2AX-MDC1 pathway is operative but becomes critical for 53BP1 recruitment to DNA-damage sites and cell survival following DSB induction when H2AX is not available. Consequently, our results suggest a role for MDC1 in activating the DDR in areas of the genome lacking or depleted of H2AX.

Induction and Repair of DNA Double-Strand Breaks in Human Cells: Dephosphorylation of Histone H2AX and its Inhibition by Calyculin A

2005 ◽  
Vol 164 (4) ◽  
pp. 514-517 ◽  
Author(s):  
Francesca Antonelli ◽  
Mauro Belli ◽  
Giacomo Cuttone ◽  
Valentina Dini ◽  
Giuseppe Esposito ◽  
...  
Keyword(s):  
Human Cells ◽  
Double Strand Breaks ◽  
Calyculin A ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Histone H2ax

scholarly journals An Oligomerized 53BP1 Tudor Domain Suffices for Recognition of DNA Double-Strand Breaks

2008 ◽  
Vol 29 (4) ◽  
pp. 1050-1058 ◽  
Author(s):  
Omar Zgheib ◽  
Kristopher Pataky ◽  
Juergen Brugger ◽  
Thanos D. Halazonetis
Keyword(s):  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Checkpoint Proteins ◽  
Strand Breaks ◽  
Histone H2ax ◽  
Dna Dsbs ◽  
Tudor Domain ◽  
Histone Core ◽  
Histone H2ax Phosphorylation ◽  
Oligomerization Domain

ABSTRACT 53BP1, the vertebrate ortholog of the budding yeast Rad9 and fission yeast Crb2/Rhp9 checkpoint proteins, is recruited rapidly to sites of DNA double-strand breaks (DSBs). A tandem tudor domain in human 53BP1 that recognizes methylated residues in the histone core is necessary, but not sufficient, for efficient recruitment. By analysis of deletion mutants, we identify here additional elements in 53BP1 that facilitate recognition of DNA DSBs. The first element corresponds to an independently folding oligomerization domain. Replacement of this domain with heterologous tetramerization domains preserves the ability of 53BP1 to recognize DNA DSBs. A second element is only about 15 amino acids long and appears to be a C-terminal extension of the tudor domain, rather than an independently functioning domain. Recruitment of 53BP1 to sites of DNA DSBs is facilitated by histone H2AX phosphorylation and ubiquitination. However, none of the 53BP1 domains/elements important for recruitment are known to bind phosphopeptides or ubiquitin, suggesting that histone phosphorylation and ubiquitination regulate 53BP1 recruitment to sites of DNA DSBs indirectly.

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