SMARCAL1 and replication stress
نویسندگان
چکیده
منابع مشابه
SMARCAL1 Resolves Replication Stress at ALT Telomeres
Cancer cells overcome replicative senescence by exploiting mechanisms of telomere elongation, a process often accomplished by reactivation of the enzyme telomerase. However, a subset of cancer cells lack telomerase activity and rely on the alternative lengthening of telomeres (ALT) pathway, a recombination-based mechanism of telomere elongation. Although the mechanisms regulating ALT are not fu...
متن کاملATR phosphorylates SMARCAL1 to prevent replication fork collapse.
The DNA damage response kinase ataxia telangiectasia and Rad3-related (ATR) coordinates much of the cellular response to replication stress. The exact mechanisms by which ATR regulates DNA synthesis in conditions of replication stress are largely unknown, but this activity is critical for the viability and proliferation of cancer cells, making ATR a potential therapeutic target. Here we use sel...
متن کاملThe annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks.
Mutations in SMARCAL1 (HARP) cause Schimke immunoosseous dysplasia (SIOD). The mechanistic basis for this disease is unknown. Using functional genomic screens, we identified SMARCAL1 as a genome maintenance protein. Silencing and overexpression of SMARCAL1 leads to activation of the DNA damage response during S phase in the absence of any genotoxic agent. SMARCAL1 contains a Replication protein...
متن کاملSMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication.
SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like1) maintains genome integrity during DNA replication. Here we investigated its mechanism of action. We found that SMARCAL1 travels with elongating replication forks, and its absence leads to MUS81-dependent double-strand break formation. Binding to specific nucleic acid substrates activates SMA...
متن کاملIdentification and Characterization of SMARCAL1 Protein Complexes
SMARCAL1 is an ATPase in the SNF2 family that functions at damaged replication forks to promote their stability and restart. It acts by translocating on DNA to catalyze DNA strand annealing, branch migration, and fork regression. Many SNF2 enzymes work as motor subunits of large protein complexes. To determine if SMARCAL1 is also a member of a protein complex and to further understand how it fu...
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ژورنال
عنوان ژورنال: Nucleus
سال: 2010
ISSN: 1949-1034,1949-1042
DOI: 10.4161/nucl.11739