ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts.

ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Research Abstract Details 

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ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Abstract Text:

Ken-ichi Yoshioka,Yoshiko Yoshioka,Peggy Hsieh,

S(N)1-type alkylating agents that produce cytotoxic O(6)-methyl-G (O(6)-meG) DNA adducts induce cell cycle arrest and apoptosis in a manner requiring the DNA mismatch repair (MMR) proteins MutSalpha and MutLalpha. Here, we show that checkpoint signaling in response to DNA methylation occurs during S phase and requires DNA replication that gives rise to O(6)-meG/T mispairs. DNA binding studies reveal that MutSalpha specifically recognizes O(6)-meG/T mispairs, but not O(6)-meG/C. In an in vitro assay, ATR-ATRIP, but not RPA, is preferentially recruited to O(6)-meG/T mismatches in a MutSalpha- and MutLalpha-dependent manner. Furthermore, ATR kinase is activated to phosphorylate Chk1 in the presence of O(6)-meG/T mispairs and MMR proteins. These results suggest that MMR proteins can act as direct sensors of methylation damage and help recruit ATR-ATRIP to sites of cytotoxic O(6)-meG adducts to initiate ATR checkpoint signaling.

ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Publishing Authors By Initials

K Yoshioka,Y Yoshioka,P Hsieh,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Intr

Journal: Molecular cell

VOLUME: 22

Page Numbers: 501-10

Journal Abbreviation: Mol. Cell

ISSN: 1097-2765

DAY: 19

MONTH: May

YEAR: 2006

ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Information

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LANGUAGE: eng

NlmUniqueID: 9802571

ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: metabolism

Chemical & Substance for Abstract: ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Information

Substance Name: MutS DNA Mismatch-Binding Protein

Registry Number: EC 3.6.1.3

Grant and Affiliation Information for ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts.

AFFILIATION: Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Country: United States

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MEDLINETA: Mol Cell

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