Skip to content
Login Register

#ATR

3 public questions tagged with this topic.

Cell Cycle Regulation

Which kinase phosphorylates Chk1 in response to replication stress?

Replication stress exposes extended single-stranded DNA regions coated by replication protein A, forming a key signaling platform. ATR kinase, recruited via ATRIP-interacting domain to RPA-ssDNA, is the principal sensor of this structure. At stalled forks, factors TopBP1, Claspin, Timeless-Tipin and Rad9-Rad1-Hus1 clamp augment ATR activation through direct binding and allosteric stimulation. Once activated, ATR directly phosphorylates checkpoint kinase Chk1 on serine residues 317 and 345 within its C-terminal regulatory domain. This modification relieves autoinhibition, enabling Chk1 catalyti

Ref: Cimprich & Cortez, ATR role in replication checkpoint, Nat Rev Mol Cell Biol 2008; NCBI Bookshelf, Replication Stress Response.

View Details
Cell Cycle Regulation

Which component of the DNA damage response (DDR) is associated with single-strand DNA breaks?

Different lesions within DNA damage response activate distinct kinase cascades tailored to repair requirements. Single-strand breaks, gaps, and regions of single-stranded DNA generated when replication forks stall at UV photoproducts or chemical adducts expose stretches of RPA-coated ssDNA that recruit ATR-ATRIP complex and auxiliary proteins TopBP1 and ETAA1. ATR, ataxia telangiectasia and Rad3-related kinase, then phosphorylates CHK1 at serine 317 and 345, leading to degradation of Cdc25A and inhibition of CDK2 to slow S-phase progression and allow repair via homologous recombination or tran

Ref: Cimprich & Cortez, Nature Rev Mol Cell Biol 2008, ATR: Essential Regulator of Genome Integrity; Zou & Elledge, Science 2003, ATR Activation.

View Details
Cell Cycle Regulation

Which kinase is activated in response to double-strand DNA breaks?

DNA double-strand breaks are among most deleterious lesions, potentially generating chromosomal translocations if unrepaired. Detection relies on sensor complex MRN composed of Mre11, Rad50, and Nbs1 that binds broken ends and recruits serine/threonine kinase ATM, ataxia telangiectasia mutated, member of PI3K-like kinase family. ATM exists as inactive dimer; upon recruitment and interaction with Nbs1 C-terminus, it autophosphorylates at serine 1981, dissociates into active monomers, and phosphorylates hundreds of targets including histone variant H2AX at serine 139 forming gamma-H2AX foci that

Ref: Abraham, Genes Dev 2001, ATM and ATR Kinases; Shiloh & Ziv, Nature Rev Mol Cell Biol 2013, ATM Signaling.

View Details