کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039250 1073039 2016 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ATRIP Deacetylation by SIRT2 Drives ATR Checkpoint Activation by Promoting Binding to RPA-ssDNA
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
ATRIP Deacetylation by SIRT2 Drives ATR Checkpoint Activation by Promoting Binding to RPA-ssDNA
چکیده انگلیسی


• SIRT2 interacts with and deacetylates ATRIP at K32 in vitro and in cells
• ATRIP deacetylation by SIRT2 promotes ATR activation and replication stress recovery
• ATRIP deacetylation by SIRT2 promotes accumulation to sites of DNA damage
• SIRT2 deacetylation of ATRIP at K32 promotes its direct binding to RPA-ssDNA

SummaryThe ataxia telangiectasia-mutated and Rad3-related (ATR) kinase checkpoint pathway maintains genome integrity; however, the role of the sirtuin 2 (SIRT2) acetylome in regulating this pathway is not clear. We found that deacetylation of ATR-interacting protein (ATRIP), a regulatory partner of ATR, by SIRT2 potentiates the ATR checkpoint. SIRT2 interacts with and deacetylates ATRIP at lysine 32 (K32) in response to replication stress. SIRT2 deacetylation of ATRIP at K32 drives ATR autophosphorylation and signaling and facilitates DNA replication fork progression and recovery of stalled replication forks. K32 deacetylation by SIRT2 further promotes ATRIP accumulation to DNA damage sites and binding to replication protein A-coated single-stranded DNA (RPA-ssDNA). Collectively, these results support a model in which ATRIP deacetylation by SIRT2 promotes ATR-ATRIP binding to RPA-ssDNA to drive ATR activation and thus facilitate recovery from replication stress, outlining a mechanism by which the ATR checkpoint is regulated by SIRT2 through deacetylation.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 14, Issue 6, 16 February 2016, Pages 1435–1447
نویسندگان
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