Induction of DNA damage by urethane in mouse testes: DNA binding and unscheduled DNA synthesis

1994 ◽  
Vol 24 (1) ◽  
pp. 68-74 ◽  
Author(s):  
Rene E. Sotomayor ◽  
Gary A. Sega ◽  
Fred Kadlubar
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Dna Synthesis ◽  
Unscheduled Dna Synthesis

scholarly journals Binding of a sequence-specific single-stranded DNA-binding factor to the simian virus 40 core origin inverted repeat domain is cell cycle regulated.

1993 ◽  
Vol 13 (1) ◽  
pp. 408-420 ◽  
Author(s):  
E P Carmichael ◽  
J M Roome ◽  
A F Wahl
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Binding ◽  
Dna Synthesis ◽  
Inverted Repeat ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Single Stranded Dna ◽  
Repeat Domain

The inverted repeat domain (IR domain) within the simian virus 40 origin of replication is the site of initial DNA melting prior to the onset of DNA synthesis. The domain had previously been shown to be bound by a cellular factor in response to DNA damage. We demonstrate that two distinct cellular components bind opposite strands of the IR domain. Replication protein A (RPA), previously identified as a single-stranded DNA binding protein required for origin-specific DNA replication in vitro, is shown to have a preference for the pyrimidine-rich strand. A newly described component, IR factor B (IRF-B), specifically recognizes the opposite strand. IRF-B binding activity in nuclear extract varies significantly with cell proliferation and the cell cycle, so that binding of IRF-B to the IR domain is negatively correlated with the onset of DNA synthesis. Loss of IRF-B binding from the nucleus also occurs in response to cellular DNA damage. UV cross-linking indicates that the core binding component of IRF-B is a protein of ca. 34 kDa. We propose that RPA and IRF-B bind opposite strands of the IR domain and together may function in the regulation of origin activation.

scholarly journals TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

2015 ◽  
Vol 210 (4) ◽  
pp. 565-582 ◽  
Author(s):  
Rune Troelsgaard Pedersen ◽  
Thomas Kruse ◽  
Jakob Nilsson ◽  
Vibe H. Oestergaard ◽  
Michael Lisby
Keyword(s):  
Dna Damage ◽  
Dna Synthesis ◽  
Chromosome Segregation ◽  
Nuclear Bodies ◽  
Genome Integrity ◽  
Unscheduled Dna Synthesis ◽  
Focus Formation ◽  
Mitotic Entry ◽  
Daughter Cells ◽  
Early Mitosis

Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis.

Binding of a sequence-specific single-stranded DNA-binding factor to the simian virus 40 core origin inverted repeat domain is cell cycle regulated

1993 ◽  
Vol 13 (1) ◽  
pp. 408-420
Author(s):  
E P Carmichael ◽  
J M Roome ◽  
A F Wahl
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Binding ◽  
Dna Synthesis ◽  
Inverted Repeat ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Single Stranded Dna ◽  
Repeat Domain

The inverted repeat domain (IR domain) within the simian virus 40 origin of replication is the site of initial DNA melting prior to the onset of DNA synthesis. The domain had previously been shown to be bound by a cellular factor in response to DNA damage. We demonstrate that two distinct cellular components bind opposite strands of the IR domain. Replication protein A (RPA), previously identified as a single-stranded DNA binding protein required for origin-specific DNA replication in vitro, is shown to have a preference for the pyrimidine-rich strand. A newly described component, IR factor B (IRF-B), specifically recognizes the opposite strand. IRF-B binding activity in nuclear extract varies significantly with cell proliferation and the cell cycle, so that binding of IRF-B to the IR domain is negatively correlated with the onset of DNA synthesis. Loss of IRF-B binding from the nucleus also occurs in response to cellular DNA damage. UV cross-linking indicates that the core binding component of IRF-B is a protein of ca. 34 kDa. We propose that RPA and IRF-B bind opposite strands of the IR domain and together may function in the regulation of origin activation.

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