Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

A large number of SNF2 family, DNA and ATP-dependent motor proteins are needed during transcription, DNA replication, and DNA repair to manipulate protein-DNA interactions and change DNA structure. SMARCAL1, ZRANB3, and HLTF are three related members of this family with specialized functions that ma...

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Bibliographic Details
Published in:Critical reviews in biochemistry and molecular biology 2017-11, Vol.52 (6), p.696-714
Main Authors: Poole, Lisa A., Cortez, David
Format: Article
Language:English
Subjects:
Animals
checkpoint
DNA - genetics
DNA - metabolism
DNA Helicases - analysis
DNA Helicases - genetics
DNA Helicases - metabolism
DNA Repair
DNA Replication
DNA-Binding Proteins - analysis
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Fork reversal
Genomic Instability
Humans
Models, Molecular
Mutation
PCNA
Protein Conformation
replication stress
RPA
Transcription Factors - analysis
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary:A large number of SNF2 family, DNA and ATP-dependent motor proteins are needed during transcription, DNA replication, and DNA repair to manipulate protein-DNA interactions and change DNA structure. SMARCAL1, ZRANB3, and HLTF are three related members of this family with specialized functions that maintain genome stability during DNA replication. These proteins are recruited to replication forks through protein-protein interactions and bind DNA using both their motor and substrate recognition domains (SRDs). The SRD provides specificity to DNA structures like forks and junctions and confers DNA remodeling activity to the motor domains. Remodeling reactions include fork reversal and branch migration to promote fork stabilization, template switching, and repair. Regulation ensures these powerful activities remain controlled and restricted to damaged replication forks. Inherited mutations in SMARCAL1 cause a severe developmental disorder and mutations in ZRANB3 and HLTF are linked to cancer illustrating the importance of these enzymes in ensuring complete and accurate DNA replication. In this review, we examine how these proteins function, concentrating on their common and unique attributes and regulatory mechanisms.
ISSN:1040-9238
1549-7798
DOI:10.1080/10409238.2017.1380597