Publications by authors named "Sudipta Lahiri"

BRCA2 is a tumor suppressor protein responsible for safeguarding the cellular genome from replication stress and genotoxicity, but the specific mechanism(s) by which this is achieved to prevent early oncogenesis remains unclear. Here, we provide evidence that BRCA2 acts as a critical suppressor of head-on transcription-replication conflicts (HO-TRCs). Using Okazaki-fragment sequencing (Ok-seq) and computational analysis, we identified origins (dormant origins) that are activated near the transcription termination sites (TTS) of highly expressed, long genes in response to replication stress.

View Article and Find Full Text PDF

Pathogenic mutations in the BRCA2 tumor suppressor gene predispose to breast, ovarian, pancreatic, prostate, and other cancers. BRCA2 maintains genome stability through homology-directed repair (HDR) of DNA double-strand breaks (DSBs) and replication fork protection. Nonsense or frameshift mutations leading to truncation of the BRCA2 protein are typically considered pathogenic; however, missense mutations resulting in single amino acid substitutions can be challenging to functionally interpret.

View Article and Find Full Text PDF

Crossing over is essential for chromosome segregation during meiosis. Protein modification by SUMO is implicated in crossover control, but pertinent targets have remained elusive. Here we identify Msh4 as a target of SUMO-mediated crossover regulation.

View Article and Find Full Text PDF

The homologous recombination (HR) pathway maintains genomic integrity by repairing DNA double-strand breaks (DSBs), single-strand DNA gaps, and collapsed replication forks. The process of HR involves strand invasion, homology search, and DNA strand exchange between paired DNA molecules. HR is critical for the high-fidelity repair of DNA DSBs in mitotic cells and for the exchange of genetic information during meiosis.

View Article and Find Full Text PDF

In many organisms, MutSγ plays a role in meiotic recombination, facilitating crossover formation between homologous chromosomes. Failure to form crossovers leads to improper segregation of chromosomes and aneuploidy, which in humans result in infertility and birth defects. To improve current understanding of MutSγ function, this study investigates the binding affinities and structures of MutSγ in complex with DNA substrates that model homologous recombination intermediates.

View Article and Find Full Text PDF

A conserved hairpin-like structure comprised of a signal peptide and early mature region initiates protein transport across the SecY or Sec61α channel in Bacteria or Archaea and Eukarya, respectively. When and how this initiator substrate hairpin forms remains a mystery. Here, we have used the bacterial SecA ATPase motor protein and SecYEG channel complex to address this question.

View Article and Find Full Text PDF