Rad54 and DNA Ligase IV Cooperate to Maintain Mammalian Chromatid Stability

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2004 Jun 4

PMID 15175260

Citations 58

Authors

Kevin D Mills

David O Ferguson

Jeroen Essers

Mark Eckersdorff

Roland Kanaar

Frederick W Alt

Affiliations

Soon will be listed here.

Abstract

Nonhomologous end joining (NHEJ) and homologous recombination (HR) represent the two major pathways of DNA double-strand break (DSB) repair in eukaryotic cells. NHEJ repairs DSBs by ligation of cognate broken ends irrespective of homologous flanking sequences, whereas HR repairs DSBs using an undamaged homologous template. Although both NHEJ and HR have been clearly implicated in the maintenance of genome stability, how these apparently independent and mechanistically distinct pathways are coordinated remains largely unexplored. To investigate the relationship between HR and NHEJ modes of DSB repair, we generated cells doubly deficient for the NHEJ factor DNA Ligase IV (Lig4) and the HR factor Rad54. We show that Lig4 and Rad54 cooperate to support cellular proliferation, repair spontaneous DSBs, and prevent chromosome and single chromatid aberrations. These findings demonstrate a role for NHEJ in the repair of DSBs that occur spontaneously during or after DNA replication, and reveal overlapping functions for NHEJ and Rad54-dependent HR in the repair of such DSBs.

Citing Articles

Synergistic Roles of Non-Homologous End Joining and Homologous Recombination in Repair of Ionizing Radiation-Induced DNA Double Strand Breaks in Mouse Embryonic Stem Cells.

van de Kamp G, Heemskerk T, Kanaar R, Essers J Cells. 2024; 13(17.

PMID: 39273031 PMC: 11393957. DOI: 10.3390/cells13171462.

The translocation activity of Rad54 reduces crossover outcomes during homologous recombination.

Sridalla K, Woodhouse M, Hu J, Scheer J, Ferlez B, Crickard J Nucleic Acids Res. 2024; 52(12):7031-7048.

PMID: 38828785 PMC: 11229335. DOI: 10.1093/nar/gkae474.

Short Double-Stranded DNA (≤40-bp) Affects Repair Pathway Choice.

Li Z, Wang Y Int J Mol Sci. 2023; 24(14).

PMID: 37511594 PMC: 10380458. DOI: 10.3390/ijms241411836.

ASTE1 cutting to block DNA end resection.

He Y, Chowdhury D Nat Cell Biol. 2021; 23(8):818-819.

PMID: 34354234 DOI: 10.1038/s41556-021-00731-9.

A Link between Replicative Stress, Lamin Proteins, and Inflammation.

Willaume S, Rass E, Fontanilla-Ramirez P, Moussa A, Wanschoor P, Bertrand P Genes (Basel). 2021; 12(4).

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