7m0b

Publication Abstract from PubMed

DNA double-strand breaks (DSBs) threaten genomic stability, since their persistence can lead to loss of critical genetic information, chromosomal translocations or rearrangements, and cell death. DSBs can be repaired through the nonhomologous end-joining pathway (NHEJ), which processes and ligates DNA ends efficiently to prevent or minimize sequence loss. Polymerase lambda (Pollambda), one of the Family X polymerases, fills sequence gaps of DSB substrates with a strict specificity for a base-paired primer terminus. There is little information regarding Pollambda's approach to engaging such substrates. We used in vitro polymerization and cell-based NHEJ assays to explore the contributions of conserved loop regions toward DSB substrate specificity and utilization. In addition, we present multiple crystal structures of Pollambda in synapsis with varying biologically relevant DSB end configurations, revealing how key structural features and hydrogen bonding networks work in concert to stabilize these tenuous, potentially cytotoxic DNA lesions during NHEJ.

Analysis of diverse double-strand break synapsis with Pollambda reveals basis for unique substrate specificity in nonhomologous end-joining.,Kaminski AM, Chiruvella KK, Ramsden DA, Bebenek K, Kunkel TA, Pedersen LC Nat Commun. 2022 Jul 1;13(1):3806. doi: 10.1038/s41467-022-31278-4. PMID:35778389^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.