* ATM-mediated phosphorylation of the chromatin remodeling enzyme BRG1 modulates DNA double-strand break repair.
- ATP-dependent chromatin remodeling complexes such as SWI/SNF (SWItch/Sucrose NonFermentable) have been implicated in DNA double-strand break (DSB) repair and damage responses. However, the regulatory mechanisms that control the function of chromatin remodelers in DNA damage response are largely unknown. Here, we show that ataxia telangiectasia mutated (ATM) mediates the phosphorylation of BRG1, the catalytic ATPase of the SWI/SNF complex that contributes to DSB repair by binding γ-H2AX-containing nucleosomes via interaction with acetylated histone H3 and stimulating γ-H2AX formation, at Ser-721 in response to DNA damage. ATM-mediated phosphorylation of BRG1 occurs rapidly and transiently after DNA damage. Phosphorylated BRG1 binds γ-H2AX-containing nucleosomes to form the repair foci. The Ser-721 phosphorylation of BRG1 is critical for binding γ-H2AX-containing nucleosomes and stimulating γ-H2AX formation and DSB repair. BRG1 binds to acetylated H3 peptides much better after phosphorylation at Ser-721 by DNA damage. However, the phosphorylation of Ser-721 does not significantly affect the ATPase and transcriptional activities of BRG1. These results, establishing BRG1 as a novel and functional ATM substrate, suggest that the ATM-mediated phosphorylation of BRG1 facilitates DSB repair by stimulating the association of this remodeler with γ-H2AX nucleosomes via enhancing the affinity to acetylated H3. Our work also suggests that the mechanism of BRG1 stimulation of DNA repair is independent of the remodeler's enzymatic or transcriptional activities.
=>1.機能, 関数, 役割, 働き, 2.機能する, 作用する, 働く, 役目を果たす, 3.社交的会合, パーティー, 儀式
Overview of noun function
The noun function has 7 senses (first 3 from tagged texts)
1. (43) function, mathematical function, single-valued function, map, mapping -- ((mathematics) a
mathematical relation such that each element of a given set (the domain of the function) is
associated with an element of another set (the range of the function))
2. (24) function, purpose, role, use -- (what something is used for; "the function of an auger is to
bore holes"; "ballet is beautiful but what use is it?")
3. (7) function, office, part, role -- (the actions and activities assigned to or required or
expected of a person or group; "the function of a teacher"; "the government must do its part"; "play
its role")
4. function -- (a relation such that one thing is dependent on another; "height is a function of
age"; "price is a function of supply and demand")
5. function -- (a formal or official social gathering or ceremony; "it was a black-tie function")
6. affair, occasion, social occasion, function, social function -- (a vaguely specified social
event; "the party was quite an affair"; "an occasion arranged to honor the president"; "a seemingly
endless round of social functions")
7. routine, subroutine, subprogram, procedure, function -- (a set sequence of steps, part of larger
computer program)
Overview of verb function
The verb function has 3 senses (first 3 from tagged texts)
1. (9) function, work, operate, go, run -- (perform as expected when applied; "The washing machine
won't go unless it's plugged in"; "Does this old car still run well?"; "This old radio doesn't work
anymore")
2. (3) serve, function -- (serve a purpose, role, or function; "The tree stump serves as a table";
"The female students served as a control group"; "This table would serve very well"; "His freedom
served him well"; "The table functions as a desk")
3. (1) officiate, function -- (perform duties attached to a particular office or place or function;
"His wife officiated as his private secretary")
--- WordNet end ---