Ricombination lesson final2 2

Recombination Overview

  • Recombination: Process involves the breaking and rejoining of parental DNA molecules to produce new DNA molecules.

Definitions and Models

  • Recombination Definitions:

    • Breaking and rejoining of DNA molecules to produce new genetic material.

Types of Recombination

  • Types of recombination:

    • Homologous recombination: General process involving sequence similarity (A+, B+, C+, A-, B-, C-).

    • Site-specific recombination: Targeted integration of DNA segments (e.g., viral, plasmid).

    • Replicative recombination: Involves transposition of DNA elements.

Mechanisms of Recombination

  • General Mechanisms:

    • Reciprocal recombination: New DNA includes genetic information from both parental molecules.

    • Homologous recombination: Repair of DSB during cellular processes in bacteria and eukaryotes (during meiosis).

Functions in Prokaryotes

  • Role in Prokaryotes:

    • Major function is to repair DSBs due to ionizing radiation or replication fork collapse.

    • Offers genetic exchange with viruses or other bacterial DNA during conjugation.

Functions in Eukaryotes

  • Role in Eukaryotes:

    • Crucial for repair of DSBs and chromosome pairing during meiosis for genetic variability.

Steps of Homologous Recombination

  • Key steps include:

    1. Alignment of homologous DNA molecules.

    2. Break introduction in the DNA strands.

    3. Generation of single-stranded DNA (ssDNA).

    4. Strand invasion to create Holliday junctions.

    5. Branch migration of Holliday junction to lengthen hybrid DNA.

    6. Resolution of Holliday junction, leading to genetic exchange.

Eukaryotic Specifics

  • Meiotic Recombination:

    • Essential for proper alignment and segregation of chromosomes.

    • Absence leads to non-disjunction and fertility issues.

  • Spo11 protein creates DSBs in eukaryotic meiosis, crucial for pairing homologous chromosomes.

Proteins Involved in Recombination

  • Key Recombination Proteins:

    • Prokaryotic: RecA protein.

    • Eukaryotic: Rad51 protein and Dcm1 (during meiosis).

  • Function of RecBCD:

    • Cleaves and processes DSBs, generating ssDNA for strand invasion by RecA.

Disease Association with Recombination

  • RecQ Helicases: Linked to human syndromes (Bloom, Werner, Rothmund-Thomson) that predispose individuals to cancers.

  • BRCA1 and BRCA2 Genes: Involved in homologous recombination; mutations increase risks for breast and ovarian cancers.

Summary of BRCA1/2 Related Cancers

  • Cancer Risks:

    • High risk of breast and ovarian cancer for women with BRCA mutations.

    • Increased risks for several other cancers in both genders.