PCL477H1-Lecture 8b to post - RAD50-Mre11-NBS1 participate...

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RAD50-Mre11-NBS1 participate in recruiting ATM to sites of double-strand breaks via interaction of ATM with NBS1 ATLD (A-T like Disease): mutations in Mre11 –very, very rare only four probands
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ATM-Chk2-p53 Dissemination of signal Damage ATM Chk2 p53 Apoptosis p21 cdc25c cdk2 G1 phase arrest cdk2 S phase arrest cdk1 G2 phase arrest cdc25a ATM accesses NBS1 and Chk2 at sites of DNA damage but outcome different phospho-NBS1: localized to sites of DNA damage phospho-Chk2: globally distributed in response to spatially restricted DNA damage
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ATR: ATM-and Rad3-related identified as a protein showing similarity to ATM (and the yeast Rad3 protein) is not activated by DNA double-strand breaks (ATM) but instead is activated by the presence of single-stranded DNA (stalled replication forks) -the following signals can activate ATR: IR, UV, ROS, Heat shock, chromium compounds, hypoxia, nutrient deficiency (considerable overlap with ATM) ATR vs. ATM: both proteins activated in a similar fashion but by different factors -ATM activated via Mre11-Rad50-Nbs1 complex at sites of DSBs -ATR activated by molecule analogous to Nbs1 called ATRIP, which ‘sees’ RPA-coated single-stranded DNA that accumulates at stalled DNA replication forks or generated by processing of initial DNA damage both proteins activate overlapping signaling pathways e.g. ATM predom. activates Chk2 whereas ATR predom. activates Chk1 ATR (and Chk1) absolutely essential for viability: not true for ATM (and Chk2)
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This note was uploaded on 12/03/2010 for the course PHAMACOLOG pcl470 taught by Professor Arnot during the Fall '10 term at University of Toronto- Toronto.

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PCL477H1-Lecture 8b to post - RAD50-Mre11-NBS1 participate...

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