Unknown

Dataset Information

0

Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase ?.

ABSTRACT: Microhomology-mediated end-joining (MMEJ) is an error-prone alternative double-strand break-repair pathway that uses sequence microhomology to recombine broken DNA. Although MMEJ has been implicated in cancer development, the mechanism of this pathway is unknown. We demonstrate that purified human DNA polymerase ? (Pol?) performs MMEJ of DNA containing 3' single-strand DNA overhangs with ?2 bp of homology, including DNA modeled after telomeres, and show that MMEJ is dependent on Pol? in human cells. Our data support a mechanism whereby Pol? facilitates end-joining and microhomology annealing, then uses the opposing overhang as a template in trans to stabilize the DNA synapse. Pol? exhibits a preference for DNA containing a 5'-terminal phosphate, similarly to polymerases involved in nonhomologous end-joining. Finally, we identify a conserved loop domain that is essential for MMEJ and higher-order structures of Pol? that probably promote DNA synapse formation.

SUBMITTER: Kent T 

PROVIDER: S-EPMC4351179 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase θ.

Kent Tatiana T   Chandramouly Gurushankar G   McDevitt Shane Michael SM   Ozdemir Ahmet Y AY   Pomerantz Richard T RT  

Nature structural & molecular biology 20150202 3

Microhomology-mediated end-joining (MMEJ) is an error-prone alternative double-strand break-repair pathway that uses sequence microhomology to recombine broken DNA. Although MMEJ has been implicated in cancer development, the mechanism of this pathway is unknown. We demonstrate that purified human DNA polymerase θ (Polθ) performs MMEJ of DNA containing 3' single-strand DNA overhangs with ≥2 bp of homology, including DNA modeled after telomeres, and show that MMEJ is dependent on Polθ in human ce  ...[more]

Similar Datasets

Unknown Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair.
| S-EPMC5466332 | biostudies-literature
Unknown Structural basis of DNA polymerase θ mediated DNA end joining.
| S-EPMC9841435 | biostudies-literature
Unknown Structure of the Helicase Domain of DNA Polymerase Theta Reveals a Possible Role in the Microhomology-Mediated End-Joining Pathway.
| S-EPMC4671958 | biostudies-literature
Unknown Poly(ADP) ribose polymerase promotes DNA polymerase theta-mediated end joining by activation of end resection.
| S-EPMC9352658 | biostudies-literature
Unknown Human papillomavirus 16 promotes microhomology-mediated end-joining.
| S-EPMC6815166 | biostudies-literature
Unknown Polymerase theta-mediated end joining of replication-associated DNA breaks in C. elegans.
| S-EPMC4032859 | biostudies-literature
Unknown ATM regulates Mre11-dependent DNA end-degradation and microhomology-mediated end joining.
| S-EPMC3040963 | biostudies-literature
Unknown Microhomology Selection for Microhomology Mediated End Joining in <i>Saccharomyces cerevisiae</i>.
| S-EPMC6523938 | biostudies-literature
Unknown The enterohemorrhagic Escherichia coli insertion sequence-excision enhancer protein is a DNA polymerase with microhomology-mediated end-joining activity.
| S-EPMC9943667 | biostudies-literature
Unknown Plant organellar DNA polymerases repair double-stranded breaks by microhomology-mediated end-joining.
| S-EPMC6451138 | biostudies-literature