2azm: Difference between revisions

Line 1:

[[Image:2azm.gif|left|200px]]<br />

[[Image:2azm.gif|left|200px]]<br /><applet load="2azm" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="2azm" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="2azm, resolution 2.41Å" />

'''Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX'''<br />

==Overview==

Histone variant H2AX phosphorylation in response to DNA damage is the, major signal for recruitment of DNA-damage-response proteins to regions of, damaged chromatin. Loss of H2AX causes radiosensitivity, genome, instability, and DNA double-strand-break repair defects, yet the, mechanisms underlying these phenotypes remain obscure. Here, we, demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX, (gammaH2AX) by specifically interacting with the phosphoepitope at the, gammaH2AX carboxyl terminus. Moreover, through a combination of, biochemical, cell-biological, and X-ray crystallographic approaches, we, reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These, data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is, the major mediator of gammaH2AX recognition following DNA damage. We, further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX, phosphorylation and is required for normal radioresistance and efficient, accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian, response to DNA damage.

Histone variant H2AX phosphorylation in response to DNA damage is the major signal for recruitment of DNA-damage-response proteins to regions of damaged chromatin. Loss of H2AX causes radiosensitivity, genome instability, and DNA double-strand-break repair defects, yet the mechanisms underlying these phenotypes remain obscure. Here, we demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX (gammaH2AX) by specifically interacting with the phosphoepitope at the gammaH2AX carboxyl terminus. Moreover, through a combination of biochemical, cell-biological, and X-ray crystallographic approaches, we reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is the major mediator of gammaH2AX recognition following DNA damage. We further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX phosphorylation and is required for normal radioresistance and efficient accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian response to DNA damage.

==Disease==

Line 11:

Line 10:

==About this Structure==

2AZM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2AZM OCA].

2AZM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AZM OCA].

==Reference==

Line 17:

Line 16:

[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Clapperton, J.A.]]

[[Category: Clapperton, J A.]]

[[Category: Jackson, S.P.]]

[[Category: Jackson, S P.]]

[[Category: Mohammad, D.]]

[[Category: Smerdon, S.J.]]

[[Category: Smerdon, S J.]]

[[Category: Stucki, M.]]

[[Category: Yaffe, M.B.]]

[[Category: Yaffe, M B.]]

[[Category: brct repeat]]

[[Category: dna damage]]

[[Category: protein-phosphopeptide complex]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 20~~:56:~~30 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:38 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:2azm.gif|left|200px]]<br />
+[[Image:2azm.gif|left|200px]]<br /><applet load="2azm" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2azm" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2azm, resolution 2.41&Aring;" />
 '''Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX'''<br />
 ==Overview==
-Histone variant H2AX phosphorylation in response to DNA damage is the, major signal for recruitment of DNA-damage-response proteins to regions of, damaged chromatin. Loss of H2AX causes radiosensitivity, genome, instability, and DNA double-strand-break repair defects, yet the, mechanisms underlying these phenotypes remain obscure. Here, we, demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX, (gammaH2AX) by specifically interacting with the phosphoepitope at the, gammaH2AX carboxyl terminus. Moreover, through a combination of, biochemical, cell-biological, and X-ray crystallographic approaches, we, reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These, data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is, the major mediator of gammaH2AX recognition following DNA damage. We, further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX, phosphorylation and is required for normal radioresistance and efficient, accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian, response to DNA damage.
+Histone variant H2AX phosphorylation in response to DNA damage is the major signal for recruitment of DNA-damage-response proteins to regions of damaged chromatin. Loss of H2AX causes radiosensitivity, genome instability, and DNA double-strand-break repair defects, yet the mechanisms underlying these phenotypes remain obscure. Here, we demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX (gammaH2AX) by specifically interacting with the phosphoepitope at the gammaH2AX carboxyl terminus. Moreover, through a combination of biochemical, cell-biological, and X-ray crystallographic approaches, we reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is the major mediator of gammaH2AX recognition following DNA damage. We further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX phosphorylation and is required for normal radioresistance and efficient accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian response to DNA damage.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-AZM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AZM OCA].
+AZM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AZM OCA].
 ==Reference==
@@ Line 17: / Line 16: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Clapperton, J.A.]]
+[[Category: Clapperton, J A.]]
-[[Category: Jackson, S.P.]]
+[[Category: Jackson, S P.]]
 [[Category: Mohammad, D.]]
-[[Category: Smerdon, S.J.]]
+[[Category: Smerdon, S J.]]
 [[Category: Stucki, M.]]
-[[Category: Yaffe, M.B.]]
+[[Category: Yaffe, M B.]]
 [[Category: brct repeat]]
 [[Category: dna damage]]
 [[Category: protein-phosphopeptide complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:56:30 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:38 2008''