Volume 30 Issue 1, January 2023

Nuclear actin polymerization helps facilitate chromosome compartment switches that can shift damaged DNA toward a nuclear environment that is favorable for DNA repair. Yet shifting multiple broken DNA strands together can also increase the likelihood of misjoining of the DNA ends and subsequent formation of translocations.

New work on DNA polymerase λ highlights its remarkable flexibility. This fits with the generally adaptable nature of the DNA-repair process in which this enzyme is involved—nonhomologous end-joining—which allows this mechanism to handle diverse types of broken DNA ends in order to restore the duplex structure, albeit with a loss of information at the join.

The mechanism controlling SWI/SNF chromatin remodeler targeting is incompletely understood. This study demonstrates that AP-1 transcription factors guide SWI/SNF to genomic regions, resulting in 3D genomic architecture alterations.

GPAT1 is a mitochondrial outer membrane protein that catalyzes the first step of glycerolipid biosynthesis. Cryo-EM structures and functional studies of human GPAT1 uncover the molecular architecture and mechanism of this important acyltransferase.

Different patterns of nucleosome exposure by developmentally indispensable pioneer transcription factors and enabling of a nucleosome remodeler complex reveal mechanisms of gene regulatory initiation within compacted chromatin.

The authors find that silent chromatin is more diverse than just facultative and constitutive heterochromatin. These inactive types have distinct three-dimensional interaction characteristics that are transposable if the underlying chromatin state is altered.

The structure of a heteromeric volume-regulated LRRC8A/C channel shows a hexameric assembly of four clustered A subunits interspersed by two C subunits, which increase the mobility of the protein, thus facilitating channel activation.

In this paper, the authors discovered and validated aminoacylated lysine ubiquitination and its writer using the genetic code expansion strategy. This non-lysine ubiquitination assembled by UBE2W can mediate rapid protein and proteome degradation.

The authors use computational protein design to stabilize the active conformation of cGAS, generating constitutively active cGAS variants that could potentiate prophylactic and therapeutic effects.

The cryo-EM structures of ESCRT-III CHMP2A and CHMP3 filaments reveal their mode of polymerization and interaction with negatively curved membrane. VPS4 constricts and cleaves the ESCRT-III CHMP2A–CHMP3 membrane tubes, thus acting as a minimal membrane fission machinery.

Yelland et al. use yeast genetics and cryo-EM to show how 2′-O-methylation on a single rRNA base gates the assembly of the ribosome via regulating interaction with the essential GTPase Nog2.

Here the authors report a genomic view of 3D chromatin reorganization following DNA damage. Movement of damaged DNA into nuclear domains, which is brought about by nuclear actin, favors error-free damage repair at the expense of rare chromosome rearrangements with oncogenic potential.

Chandramouly et al. discover that human Polλ exhibits robust microhomology-mediated end-joining (MMEJ) activity like PolΦ. Polλ promotes MMEJ in mammalian cells independently of essential nonhomologous end-joining factors LIG4/XRCC4 and Polq, which indicates a distinct Polλ-dependent MMEJ mechanism.

Kavlashvili et al. use a new in vitro approach to show that uncoupled replication forks can cause fork reversal and nascent strand degradation. Both processes occur without loss of the replisome from DNA and degradation involves multiple steps.