Role and Regulation of the RECQL4 Family during Genomic Integrity Maintenance

Abstract

RECQL4 is a member of the evolutionarily conserved RecQ family of 3’ to 5’ DNA helicases. RECQL4 is critical for maintaining genomic stability through its functions in DNA repair, recombination, and replication. Unlike many DNA repair proteins, RECQL4 has unique functions in many of the central DNA repair pathways such as replication, telomere, double-strand break repair, base excision repair, mitochondrial maintenance, nucleotide excision repair, and crosslink repair. Consistent with these diverse roles, mutations in RECQL4 are associated with three distinct genetic diseases, which are characterized by developmental defects and/or cancer predisposition. In this review, we provide an overview of the roles and regulation of RECQL4 during maintenance of genome homeostasis.

Germline NUP98 Variants in Two Siblings with a Rothmund–Thomson-Like Spectrum: Protein Functional Changes Predicted by Molecular Modeling

“…RTS2 is an autosomal recessive disorder caused by RECQL4 gene (OMIM*603780) mutations, which account for 60% of RTS cases [ 18 , 19 ]. RECQL4 encodes the member Q4 of the RecQ family of ATP-dependent DNA helicases, which play a key role in genome maintenance and stability [ 21 ]. To perform genetic analyses, informed consent was obtained from all the participants who were enrolled in the study.…”

“…WS on the other hand shows a marked overlap to RTS2, as the defects of both RECQL3 and RECQL4 DNA helicases, the caretakers of the genome, impair the essential pathways of DNA replication, recombination, repair, telomere maintenance, and chromosome segregation. Both syndromes are characterized by chromosomal instability leading to cancer [ 21 ].…”

DNA Repair and Therapeutic Strategies in Cancer Stem Cells

“…Likewise, transcriptomic analysis of cervical cancers showed increased expression in tumour cells compared to matched normal tissues of the RBP SRSF6, and that this corresponded with an increase in alternative splicing of DDR genes [ 218 ]. Intriguingly, SRSF1 binds to and stabilises RECQL4 mRNA which is important because RECQL4 is a master regulator of genome stability through regulating DNA replication and multiple DNA repair pathways, including c-NHEJ, HR, BER and NER [ 219 , 220 ]. RECQL4 expression was elevated in GSCs compared to bulk tumour cells, which was functionally relevant because knockdown reduced GSC proliferation and induced spontaneous DNA damage [ 221 ].…”

The DNA damage response - from cell biology to human disease

“…Patients with mutations in the RECQ family of DNA helicases BLM, RECQL4, and WRN present with progeroid syndromes [95] . The BLM helicase suppresses recombination and maintains genome stability [96,97] , RECQL4 participates in DNA replication and repair [98] , and the WRN helicase manages replication stress and telomere stability [99] . Mutations in BLM cause BS, in which patients present with a shortened lifespan and early presentation of age-related diseases, including diabetes, chronic obstructive pulmonary disease, and cancer [100] .…”