{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bai G"],"funding":["Swiss National Science Foundation","Cancer Research UK","European Research Council","NIEHS NIH HHS","Medical Research Council","NCI NIH HHS","Wellcome Trust","NIGMS NIH HHS","NIH HHS"],"pagination":["3044-3060.e11"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11366124"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["84(16)"],"pubmed_abstract":["G-quadruplexes (G4s) form throughout the genome and influence important cellular processes. Their deregulation can challenge DNA replication fork progression and threaten genome stability. Here, we demonstrate an unexpected role for the double-stranded DNA (dsDNA) translocase helicase-like transcription factor (HLTF) in responding to G4s. We show that HLTF, which is enriched at G4s in the human genome, can directly unfold G4s in vitro and uses this ATP-dependent translocase function to suppress G4 accumulation throughout the cell cycle. Additionally, MSH2 (a component of MutS heterodimers that bind G4s) and HLTF act synergistically to suppress G4 accumulation, restrict alternative lengthening of telomeres, and promote resistance to G4-stabilizing drugs. In a discrete but complementary role, HLTF restrains DNA synthesis when G4s are stabilized by suppressing primase-polymerase (PrimPol)-dependent repriming. Together, the distinct roles of HLTF in the G4 response prevent DNA damage and potentially mutagenic replication to safeguard genome stability."],"journal":["Molecular cell"],"pubmed_title":["HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability."],"pmcid":["PMC11366124"],"funding_grant_id":["CC2098","R35 GM136401","310030","207588","R56 ES016486","205199","T32 GM008320","101018257","R01 ES016486","R01 GM116616","CC2057","P01 CA092584","S10 OD026899"],"pubmed_authors":["Endres T","Kuhbacher U","Crossley MP","Cimprich KA","Greer BH","Cejka P","Boulton SJ","Eichman BF","Newton MD","Dello Stritto MR","Sathirachinda A","Peacock EM","Stanage T","Mengoli V","Lungu R","Cortez D","Bai G"],"additional_accession":[]},"is_claimable":false,"name":"HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability.","description":"G-quadruplexes (G4s) form throughout the genome and influence important cellular processes. Their deregulation can challenge DNA replication fork progression and threaten genome stability. Here, we demonstrate an unexpected role for the double-stranded DNA (dsDNA) translocase helicase-like transcription factor (HLTF) in responding to G4s. We show that HLTF, which is enriched at G4s in the human genome, can directly unfold G4s in vitro and uses this ATP-dependent translocase function to suppress G4 accumulation throughout the cell cycle. Additionally, MSH2 (a component of MutS heterodimers that bind G4s) and HLTF act synergistically to suppress G4 accumulation, restrict alternative lengthening of telomeres, and promote resistance to G4-stabilizing drugs. In a discrete but complementary role, HLTF restrains DNA synthesis when G4s are stabilized by suppressing primase-polymerase (PrimPol)-dependent repriming. Together, the distinct roles of HLTF in the G4 response prevent DNA damage and potentially mutagenic replication to safeguard genome stability.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-06-02T03:58:21.516Z","creation":"2025-04-06T01:56:45.931Z"},"accession":"S-EPMC11366124","cross_references":{"pubmed":["39142279"],"doi":["10.1016/j.molcel.2024.07.018"]}}