Shan Zha

Catalytically inactive PARP1 protein drives PARP inhibitor induced hematological toxicity

This study shows that catalytically inactive PARP1, not PARP2, is responsible for PARP inhibitor-induced hematological toxicity in mice.

Programmed Clonal Expansion Drives an ATM-Dependent Vulnerability Underlying Preferential Lymphocyte Depletion and Myeloid Bias Following DNA Damage

The paper identifies programmed clonal expansion during V(D)J recombination as an ATM-dependent vulnerability causing preferential lymphocyte depletion and myeloid bias after DNA damage.

PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation

This study identifies context-dependent roles of PARP1 in regulating Okazaki fragment maturation by controlling 5' flap dynamics and DNA ligation processes.

PARG inhibition sequesters nuclear PAR-binding proteins, including XRCC1 and its partners, into nuclear condensates to elicit cytotoxicity

The paper shows PARG inhibition causes nuclear condensates that sequester PAR-binding repair proteins, leading to cytotoxicity and identifying PAR-binding factor loss as potential biomarkers for PARG-targeted therapy.

Primate-specific adaptation of Ku protects transcriptomic integrity by suppressing Alu-mediated alternative splicing

This study shows that primate-specific Ku adaptation suppresses Alu-mediated alternative splicing, maintaining transcriptomic integrity and linking Ku function to brain development and disease.

Scalable co-sequencing of RNA and DNA from individual nuclei

This paper introduces DEFND-seq, a method for jointly profiling DNA and RNA from individual nuclei, enabling analysis of gene expression with copy number and SNV associations.

XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites

This study shows that XRCC1 facilitates PARP1-mediated recruitment of PARP2 to DNA damage sites through PAR binding and interaction with PARP2.

Ku suppresses RNA-mediated innate immune responses in human cells to accommodate primate-specific Alu expansion.

The paper shows Ku suppresses RNA-mediated innate immune responses in human cells, enabling primate-specific Alu element expansion by reducing dsRNA-induced inflammation.

Inactive Parp2 causes Tp53-dependent lethal anemia by blocking replication-associated nick ligation in erythroblasts

The paper shows that inactive PARP2 causes Tp53-dependent lethal anemia by blocking replication-associated nick ligation in erythroblasts, explaining PARPi-induced hematological toxicities.

The KU70-SAP domain has an overlapping function with DNA-PKcs in limiting the lateral movement of KU along DNA

This study identifies the SAP domain of Ku70 as limiting KU lateral movement on DNA, with DNA-PKcs partially masking this function in NHEJ.

Inactive PARP1 causes embryonic lethality and genome instability in a dominant-negative manner.

This study shows that catalytically inactive PARP1 causes embryonic lethality and genome instability in a dominant-negative manner, revealing its severe impact on normal tissues.

ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.

This study shows ATR kinase prevents replication resource exhaustion in early S phase, supporting normal cell proliferation by regulating origin firing.

ARP2/3- and resection-coupled genome reorganization facilitates translocations

The paper shows that ARP2/3-dependent nuclear actin polymerization and DNA end-resection coordinate genome reorganization to facilitate homology-directed repair and prevent translocations.