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The bacterial MRE11-RAD50 and DNA2-WRN homologs process replication forks at distinct and separate loci on the chromosome.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: The bacterial MRE11-RAD50 and DNA2-WRN homologs process replication forks at distinct and separate loci on the chromosome.
Συγγραφείς: Spolek RL; Department of Biology, Portland State University, OR, USA., Christian PYH; Department of Biology, Portland State University, OR, USA., Courcelle CT; Department of Biology, Portland State University, OR, USA., Courcelle J; Department of Biology, Portland State University, OR, USA.
Πηγή: FEBS letters [FEBS Lett] 2026 Feb; Vol. 600 (4), pp. 451-466. Date of Electronic Publication: 2025 Oct 30.
Τύπος έκδοσης: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: John Wiley & Sons Ltd Country of Publication: England NLM ID: 0155157 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3468 (Electronic) Linking ISSN: 00145793 NLM ISO Abbreviation: FEBS Lett Subsets: MEDLINE
Imprint Name(s): Publication: Jan. 2016- : West Sussex : John Wiley & Sons Ltd.
Original Publication: Amsterdam, North-Holland on behalf of the Federation of European Biochemical Societies.
Ιατρικοί όροι (MeSH): Chromosomes, Bacterial*/metabolism , Escherichia coli*/metabolism , Escherichia coli Proteins*/metabolism , MRE11 Homologue Protein*/metabolism , DNA Damage Tolerance*, Acid Anhydride Hydrolases ; Werner Syndrome Helicase ; DNA-Binding Proteins ; DNA Helicases ; Deoxyribonucleases ; Exonucleases
Περίληψη: Human BRCA2 protects the DNA when replication forks stall, whereas MRE11-RAD50 and DNA2-WRN process or partially degrade these substrates. When mutated, these genes result in distinct genetic instabilities and cancers, arguing they have unique, not redundant, functions. Escherichia coli encodes functional homologs of MRE11-RAD50 (SbcC-SbcD), DNA2-WRN (RecJ-RecQ), and BRCA2 (RecF). Here, we use 2-dimensional gels, pulse-labelling, and replication-profiling analysis to show the bacterial homologs act at distinct substrates and loci on the chromosome. Whereas RecF and RecJ-RecQ protect and process DNA at arrested replication forks to facilitate repair, RecBCD and SbcC-SbcD protect and process DNA at sites where forks converge. Comparing the assays used in E. coli to human cells, we consider whether these cellular roles may be functionally conserved. Impact statement BRCA2, MRE11-RAD50, and WRN-DNA2 encode human proteins that process replication forks and result in distinct genetic instabilities and cancers when mutated. Here, we show their bacterial homologs act on unique replication fork substrates-those at DNA damage sites or as replication completes, and discuss their possible functional conservation in humans.
(© 2025 Federation of European Biochemical Societies.)
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Grant Information: R21 ES034880 United States ES NIEHS NIH HHS; R16 GM145543 United States GM NIGMS NIH HHS
Contributed Indexing: Keywords: DNA replication; DNA2‐WRN; MRE11–RAD50; RecJ–RecQ; SbcC–SbcD
Molecular Sequence: BioProject PRJNA1335257
Substance Nomenclature: EC 3.6.4.12 (DNA2 protein, human)
0 (Escherichia coli Proteins)
EC 3.1.- (MRE11 Homologue Protein)
0 (MRE11 protein, human)
EC 3.6.- (RAD50 protein, human)
0 (SbcC protein, E coli)
EC 3.1.- (sbcD protein, E coli)
EC 3.6.4.12 (WRN protein, human)
EC 3.6.- (Acid Anhydride Hydrolases)
EC 3.6.4.12 (Werner Syndrome Helicase)
0 (DNA-Binding Proteins)
EC 3.6.4.- (DNA Helicases)
EC 3.1.- (Deoxyribonucleases)
EC 3.1.- (Exonucleases)
Entry Date(s): Date Created: 20251031 Date Completed: 20260224 Latest Revision: 20260821
Update Code: 20260822
PubMed Central ID: PMC13050550
DOI: 10.1002/1873-3468.70211
PMID: 41168947
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1873-3468
DOI:10.1002/1873-3468.70211